2024-03-28T19:04:36Zhttps://minerva.usc.es/oai/requestoai:minerva.usc.es:10347/233432023-07-10T06:12:09Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Cambeiro Cambeiro, Fermín
author
López Estévez, Susana
author
Varela Carrete, Jesús Ángel
author
Saá Rodríguez, Carlos
author
2014
A novel synthesis of 2‐vinyldihydropyrans and dihydro‐1,4‐oxazines (morpholine derivatives) from alkynals and alkynones has been developed. The cyclizations require a mild generation of catalytic ruthenium carbenes from terminal alkynes and (trimethylsilyl)diazomethane followed by trapping with carbonyl nucleophiles. Mechanistic aspects of the new cyclizations are discussed.
Cambeiro, F., López, S., Varela, J. A., Saá, C. (2014). Vinyl Dihydropyrans and Dihydrooxazines: Cyclizations of Catalytic Ruthenium Carbenes Derived from Alkynals and Alkynones. Angew. Chem. Int. Ed., 53, 23, 5959-5963
1433-7851
http://hdl.handle.net/10347/23343
10.1002/anie.201400675
1521-3773
Alkynes
Carbenes
Cyclization
Heterocycles
Ruthenium
Vinyl Dihydropyrans and Dihydrooxazines: Cyclizations of Catalytic Ruthenium Carbenes Derived from Alkynals and Alkynones
oai:minerva.usc.es:10347/233542023-07-10T06:12:59Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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dc
Martínez Yáñez, Nuria
author
Suárez Rivero, Jaime
author
Cajaraville Leiro, Ana
author
Varela Carrete, Jesús Ángel
author
Saá Rodríguez, Carlos
author
2019
A novel and mild Rh(III)-catalyzed [5+2] oxidative annulation between cyclic arylguanidines and alkynes efficiently affords 1,3-benzodiazepines (pentacyclic guanidines). The use of O2 as the sole oxidant in place commonly used metal oxidants such as AgOAc clearly improves the efficiency of the oxidative annulation process. The mechanism of the cycloaddition most likely involves the formation of an eight-membered rhodacycle. DFT calculations support a striking mechanistic proposal for the [5+2] oxidative annulation.
Martínez-Yáñez, N., Suárez, J., Cajaraville, A., Varela, J. A., Saá, C. (2019). Rh(III)-Catalyzed [5+2] Oxidative Annulation of Cyclic Arylguanidines and Alkynes to 1,3-Benzodiazepines. A Striking Mechanistic Proposal from DFT. Org. Lett. 21, 6, 1779-1783
1523-7060
http://hdl.handle.net/10347/23354
10.1021/acs.orglett.9b00354
1523-7052
Alkynes
Arylguanidines
1,3-Benzodiazepines
Oxidative Annulation
Rhodium
Rh(III)-Catalyzed [5+2] Oxidative Annulation of Cyclic Arylguanidines and Alkynes to 1,3-Benzodiazepines. A Striking Mechanistic Proposal from DFT
oai:minerva.usc.es:10347/184622023-07-10T06:17:02Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Destito, Paolo
author
Sousa Castillo, Ana
author
Rodríguez Couceiro, José
author
López García, Fernando
author
Correa Duarte, Miguel Ángel
author
Mascareñas Cid, José Luis
author
2019
We describe the fabrication of hollow microspheres consisting of mesoporous silica nanoshells decorated with an inner layer of palladium nanoparticles and their use as Pd-nanoreactors in aqueous media. These palladium-equipped capsules can be used to promote the uncaging of propargyl-protected phenols, as well as Suzuki–Miyaura cross-coupling, in water and at physiologically compatible temperatures. Importantly, the depropargylation reaction can be accomplished in a bioorthogonal manner in the presence of relatively high concentrations of biomolecular components and even in the presence of mammalian cells
Destito, P., Sousa-Castillo, A., Couceiro, J., López, F., Correa-Duarte, M., & Mascareñas, J. (2019). Hollow nanoreactors for Pd-catalyzed Suzuki–Miyaura coupling and O-propargyl cleavage reactions in bio-relevant aqueous media. Chemical Science, 10(9), 2598-2603. doi: 10.1039/c8sc04390f
2041-6539
http://hdl.handle.net/10347/18462
10.1039/c8sc04390f
Hollow nanoreactors for Pd-catalyzed Suzuki–Miyaura coupling and O-propargyl cleavage reactions in bio-relevant aqueous media
oai:minerva.usc.es:10347/170022020-06-15T11:24:30Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Ozores, Lionel Haxel
author
Amorín López, Manuel
author
Granja Guillán, Juan Ramón
author
2016-12-20
A new capsule based on a β-sheet self-assembling cyclic peptide with the ability to recognize and release several guests is described. The host structure is composed of two self-complementary α,γ-cyclic peptides bearing a Zn porphyrin cap that is used for the selective recognition of the guest. The two components are linked through two dynamic covalent bonds. The combination of binding forces, including hydrogen bonding, metal coordination, and dynamic hydrazone bonds, allows the reversible recognition of long bipyridine guests. The affinity for these ligands showed a strong dependence on the guest length. Delivery of the encapsulated ligand can be achieved by hydrolysis of hydrazones to disrupt the sandwich complex structure
Ozores, L.H., Amorín, M., & Granja, J. (2017). Self-Assembling Molecular Capsules Based on α,γ-Cyclic Peptides. Journal of the American Chemical Society, 2017, 139 (2), pp 776–784. http://dx.doi.org/10.1021/jacs.6b10456
0002-7863
http://hdl.handle.net/10347/17002
10.1021/jacs.6b10456
1520-5126
Self-assembling
Cyclic peptide
Supramolecular chemistry
Self-assembling molecular capsules based on alpha, gamma-Cyclic peptides
oai:minerva.usc.es:10347/227862023-07-10T06:21:38Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Mosquera Mosquera, Jesús
author
García, Isabel
author
Henriksen-Lacey, Malou
author
Martínez Calvo, Miguel
author
Dhanjani, Mónica
author
Mascareñas Cid, José Luis
author
Liz-Marzán, Luis M.
author
2020
When nanoparticles (NPs) are exposed to biological media, proteins are adsorbed, forming a so-called protein corona (PC). This cloud of protein aggregates hampers the targeting and transport capabilities of the NPs, thereby compromising their biomedical applications. Therefore, there is a high interest in the development of technologies that allow control over PC formation, as this would provide a handle to manipulate NPs in biological fluids. We present a strategy that enables the reversible disruption of the PC using external stimuli, thereby allowing a precise regulation of NP cellular uptake. The approach, demonstrated for gold nanoparticles (AuNPs), is based on a biorthogonal, supramolecular host–guest interactions between an anionic dye bound to the AuNP surface and a positively charged macromolecular cage. This supramolecular complex effectively behaves as a zwitterionic NP ligand, which is able not only to prevent PC formation but also to disrupt a previously formed hard corona. With this supramolecular stimulus, the cellular internalization of AuNPs can be enhanced by up to 30-fold in some cases, and even NP cellular uptake in phagocytic cells can be regulated. Additionally, we demonstrate that the conditional cell uptake of purposely designed gold nanorods can be used to selectively enhance photothermal cell death
ACS Nano 2020, 14, 5, 5382–5391
1936-0851
http://hdl.handle.net/10347/22786
10.1021/acsnano.9b08752
1936-086X
Cell uptake
Metal nanoparticles
Gold
Colloids
Assays
Protein corona
Gold nanoparticles
Host−guest chemistry
Cellular uptake
Photothermal therapy
Reversible Control of Protein Corona Formation on Gold Nanoparticles Using Host–Guest Interactions
oai:minerva.usc.es:10347/292392022-10-15T02:02:43Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Seoane Fernández, Andrés
author
Mascareñas Cid, José Luis
author
2022
Transition-metal catalyzed reactions are being increasingly used in biological contexts and even in living cells and organisms. Most of the processes so far developed rely on the ability of metal complexes to bind and activate unsaturated systems in a bioorthogonal way. The reactions are often tracked by fluorescence microscopy, by using reaction probes that emit light only after the reaction
Eur. J. Org. Chem. 2022, e202200118
1434-193X
http://hdl.handle.net/10347/29239
10.1002/ejoc.202200118
1099-0690
Biocatalysis
Bioorthogonal
Chemical biology
Cell biology
Organometallic catalysis
Exporting homogeneous transition metal catalysts to biological habitats
oai:minerva.usc.es:10347/197532023-07-10T06:17:11Zcom_10347_2988com_10347_2889com_10347_227com_10347_2921com_10347_2891com_10347_2888col_10347_11762col_10347_15784
00925njm 22002777a 4500
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Feliu, Neus
author
Docter, Dominic
author
Heine, Markus
author
Pino, Pablo del
author
Ashraf, Sumaira
author
Kolosnjaj-Tabi, Jelena
author
Macchiarini, Paolo
author
Nielsen, Peter
author
Alloyeau, Damien
author
Gazeau, Florence
author
Stauber, Roland H.
author
Parak, Wolfgang J.
author
2016
What happens to inorganic nanoparticles (NPs), such as plasmonic gold or silver, superparamagnetic iron
oxide, or fluorescent quantum dot NPs after they have been administrated to a living being? This review
discusses the integrity, biodistribution, and fate of NPs after in vivo administration. The hybrid nature of the
NPs is described, conceptually divided into the inorganic core, the engineered surface coating comprising of
the ligand shell and optionally also bio-conjugates, and the corona of adsorbed biological molecules. Empirical
evidence shows that all of these three compounds may degrade individually in vivo and can drastically modify
the life cycle and biodistribution of the whole heterostructure. Thus, the NPs may be decomposed into
different parts, whose biodistribution and fate would need to be analyzed individually. Multiple labeling and
quantification strategies for such a purpose will be discussed. All reviewed data indicate that NPs in vivo should
no longer be considered as homogeneous entities, but should be seen as inorganic/organic/biological nanohybrids with complex and intricately linked distribution and degradation pathways
Chem. Soc. Rev., 2016,45, 2440-2457
0306-0012
http://hdl.handle.net/10347/19753
10.1039/C5CS00699F
1460-4744
In vivo degeneration and the fate of inorganic nanoparticles
oai:minerva.usc.es:10347/213022023-07-10T06:17:18Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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González Bello, Concepción
author
2019
The ability of antibiotics to cure bacterial infections is at a serious risk due to the emergence and worldwide spread of superbugs. A lack of innovation and investment for almost 50 years has led to significant efforts currently being devoted to find alternative and innovative therapies to face this challenge. This short review highlights some of the recent efforts to develop synthetic small molecules with anti-infective activity. This article is focused on those compounds that, when co-administered with an antibiotic, enhance the antimicrobial action of the drug, as well as compounds that target unexplored objectives for bacterial survival. Selected examples are provided.
González-Bello, C. (2019). Recently developed synthetic compounds with anti-infective activity. Current Opinion In Pharmacology, 48, 17-23. doi: 10.1016/j.coph.2019.03.004
1471-4892
http://hdl.handle.net/10347/21302
10.1016/j.coph.2019.03.004
1471-4973
Antibiotics
Bacterium
Superbugs
Recently developed synthetic compounds with anti-infective activity
oai:minerva.usc.es:10347/213292023-07-10T06:18:12Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
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Pernas Marín, Marina
author
Blanco Rodríguez, Beatriz
author
Lence Quintana, Emilio José
author
Thompson, Paul
author
Hawkins, Alastair R.
author
González Bello, Concepción
author
2019
Diverse rigidified shikimic acids derivatives, which are stable mimetics of the high-energy conformation of shikimic acid, have been synthesized to enhance inhibitor efficacy against shikimate kinase enzyme (SK), an attractive target for antibiotic drug discovery. The synthesis of the reported conformationally restricted shikimic acid derivatives was carried out by ring-closing metathesis of allyloxy vinyl derivatives as the key step. The rigidification of the ligand conformation was used to maximize the effectiveness of the substituents introduced in the ether carbon bridge of the scaffold by pre-orienting their interaction with key residues and enzyme domains that are essential for catalysis and enzyme motion. Molecular Dynamics simulation studies on the enzyme/ligand complexes revealed marked differences in the positioning of the ligand substituent in the active site of the two enzymes studied (SK from Mycobacterium tuberculosis and Helicobacter pylori) and this explains their greater efficacy against one of the enzymes. This enhancement is due to the distinct induced-fit motion of the two homologous enzymes. A 20-fold improvement against the H. pylori enzyme was achieved by the introduction of a CH2OEt group in the rigid ether bridge of the reported shikimic acid analogs
Pernas, Marina, Blanco, Beatriz, Lence, Emilio, Thompson, Paul, Hawkinsb, AlastairR., González Bello, Concepción (2019). Synthesis of rigidified shikimic acid derivatives by ring-closing metathesis to imprint inhibitor efficacy against shikimate kinase enzyme. "Organic Chemistry Frontiers" vol. 6, 2514
http://hdl.handle.net/10347/21329
10.1039/c9qo00562e
2052-4129
Shikimic acid
Shikimate kinase enzyme
Synthesis of rigidified shikimic acid derivatives by ring-closing metathesis to imprint inhibitor efficacy against shikimate kinase enzyme
oai:minerva.usc.es:10347/239872023-07-10T06:18:17Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Velasco Rubio, Álvaro
author
Varela Carrete, Jesús Ángel
author
Saá Rodríguez, Carlos
author
2020
Benzazepines and benzodiazepines, benzofused seven-membered N-heterocycles, compose an important family of natural products and pharmaceuticals. Although certainly important and effectives, classical synthetic methods of these cyclic compounds involve methodologies that often require multistep procedures, with generation of waste materials and lack of sustainability. By contrast, cycloadditions based on transition metal catalyzed C-H bond activations (oxidative annulations) have emerged as appealing strategies for more sustainable synthetic processes. In this review, we focus our attention to describe the state-of-the-art transition-metal catalyzed annulations via C-H activations to benzazepines and benzodiazepines.
Velasco-Rubio, A., Varela J. A., Saá C. (2020). Recent Advances in Transition-Metal Catalyzed Oxidative Annulations to Benzazepines and Benzodiazepines. Adv. Synth. Catal., 362, 22, 4861-4875
1615-4150
http://hdl.handle.net/10347/23987
10.1002/adsc.202000808
1615-4169
Benzazepine
Benzodiazepine
C-H activation
Oxidative annulation
Transition-metal catalyst
Recent Advances in Transition-Metal Catalyzed Oxidative Annulations to Benzazepines and Benzodiazepines
oai:minerva.usc.es:10347/159622023-07-10T06:12:17Zcom_10347_2988com_10347_2889com_10347_227com_10347_2919com_10347_2891com_10347_2888com_10347_2925col_10347_11762col_10347_10699col_10347_9937
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Langenberg Pérez, Eric
author
Ferreiro Vila, Elías
author
Leborán Alvarez, Víctor
author
Fumega, Adolfo
author
Pardo, Victor
author
Rivadulla Fernández, José Francisco
author
2016-10
The temperature dependence of the thermal conductivity of 27 different single crystal oxides is reported from ≈20 K to 350 K. These crystals have been selected among the most common substrates for growing epitaxial thin-film oxides, spanning over a range of lattice parameters from ≈3.7 Å to ≈12.5 Å. Different contributions to the phonon relaxation time are discussed on the basis of the Debye model. This work provides a database for the selection of appropriate substrates for thin-film growth according to their desired thermal properties, for applications in which heat management is important
http://hdl.handle.net/10347/15962
10.1063/1.4966220
2166-532X
Thermal conductivity
Dielectric oxides
Vacancies
Epitaxy
Phonons
Analysis of the temperature dependence of the thermal conductivity of insulating single crystal oxides
oai:minerva.usc.es:10347/289812022-08-03T02:02:45Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Gómez González, Jacobo
author
Martínez Castro, Laura
author
Tolosa Barrilero, Juan
author
Alcalde Ordóñez, Ana
author
Learte Aymamí, Soraya
author
Mascareñas Cid, José Luis
author
García Martínez, Joaquín C.
author
Martínez Costas, José Manuel
author
Maréchal, Jean-Didier
author
Vázquez Sentís, Marco Eugenio
author
2022
Non-canonical DNA structures, particularly 3-way junctions (3WJs) that are transiently formed during DNA replication, have recently emerged as promising chemotherapeutic targets. Here, we describe a new approach to target 3WJs that relies on the cooperative and sequence selective recognition of A/T-rich duplex DNA branches by three AT-Hook peptides attached to a three-fold symmetric and fluorogenic 1,3,5-tristyrylbenzene core
Gomez-Gonzalez, J.; Martinez-Castro, L.; Tolosa-Barrilero, J.; Alcalde-Ordoñez, A.; LearteAymamí, S.; Mascareñas, J. L.; García-Martínez, J. C.; Martínez-Costas, J.; Maréchal, J.-D.; Vázquez López, M.; Vázquez, M. E. (2022), Selective recognition of A/T-rich DNA 3-way junctions with a three-fold symmetric tripeptide. Chem. Commun., 58: 7769-7772. doi: 10.1039/D2CC02874C
1364-548X
http://hdl.handle.net/10347/28981
10.1039/D2CC02874C
Selective recognition of A/T-rich DNA 3-way junctions with a three-fold symmetric tripeptide
oai:minerva.usc.es:10347/247522023-07-10T06:21:34Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
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Jiménez Cavero, Pilar
author
Lucas, Irene
author
Bugallo Ferrón, David
author
López Bueno, Carlos
author
Ramos Amigo, Rafael Enrique
author
Algarabel, Pedro Antonio
author
Ibarra, Manuel Ricardo
author
Rivadulla Fernández, José Francisco
author
Morellón, Luis
author
2021
We report the disentanglement of bulk and interfacial contributions to the thermally excited magnon spin current in the spin Seebeck effect
under static heating. For this purpose, we have studied the dependence of the inverse spin Hall voltage and the thermal conductivity on the
magnetic layer thickness. Knowledge of these quantities allows us to take into account the influence of both sources of thermal spin current
in the analysis of the voltage dependence. The magnetic layer thickness modulates the relative magnitude of the involved thermal drops for a
fixed total thermal difference throughout the sample. In the end, we attain the separate contributions of both sources of thermal spin
current—bulk and interfacial—and obtain the value of the thermal magnon accumulation length scale in maghemite, which we find to be
29(1) nm. According to our results, bulk magnon accumulation dominates the spin Seebeck effect in our studied range of thicknesses, but
the interfacial component is by no means negligible
Appl. Phys. Lett. 118, 092404 (2021); https://doi.org/10.1063/5.0038192
0003-6951
http://hdl.handle.net/10347/24752
10.1063/5.0038192
1077-3118
Quantification of the interfacial and bulk contributions to the longitudinal spin Seebeck effect
oai:minerva.usc.es:10347/169142020-01-31T07:44:20Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
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Espinosa-García, Joaquín
author
Fernández-Ramos, Antonio
author
Suleimanov, Y. V.
author
Corchado, J.C.
author
2014-01-02
The hydrogen abstraction reaction of fluorine with ammonia represents a true chemical challenge because it is very fast, is followed by secondary abstraction reactions, which are also extremely fast, and presents an experimental/theoretical controversy about rate coefficients. Using a previously developed full-dimensional analytical potential energy surface, we found that the F + NH3 → HF + NH2 system is a barrierless reaction with intermediate complexes in the entry and exit channels. In order to understand the reactivity of the title reaction, thermal rate coefficidents were calculated using two approaches: ring polymer molecular dynamics and quasi-classical trajectory calculations, and these were compared with available experimental data for the common temperature range 276–327 K. The theoretical results obtained show behavior practically independent of temperature, reproducing Walther–Wagner’s experiment, but in contrast with Persky’s more recent experiment. However, quantitatively, our results are 1 order of magnitude larger than those of Walther–Wagner and reasonably agree with the Persky at the lowest temperature, questioning so Walther−Wagner’s older data. At present, the reason for this discrepancy is not clear, although we point out some possible reasons in the light of current theoretical calculations
Espinosa-Garcia, J., Fernandez-Ramos, A., Suleimanov, Y., & Corchado, J. (2014). Theoretical Kinetics Study of the F(2P) + NH3 Hydrogen Abstraction Reaction. The Journal Of Physical Chemistry A, 118(3), 554-560. doi: 10.1021/jp4118453
1089-5639
http://hdl.handle.net/10347/16914
10.1021/jp4118453
1520-5215
Theoretical Kinetics Study of the F(2P) + NH3 Hydrogen Abstraction Reaction
oai:minerva.usc.es:10347/303292023-03-17T03:03:25Zcom_10347_2988com_10347_2889com_10347_227com_10347_2904com_10347_2890com_10347_2888com_10347_2927com_10347_2891col_10347_11762col_10347_12265col_10347_12292
00925njm 22002777a 4500
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Booth, Richard
author
Insua López, Ignacio
author
Ahmed, Sahnawaz
author
Rioboo Vidal, Alicia
author
Montenegro García, Javier
author
2021
One-dimensional (1D) supramolecular polymers are commonly found in natural and synthetic systems to prompt functional responses that capitalise on hierarchical molecular ordering. Despite amphiphilic self-assembly being significantly studied in the context of aqueous encapsulation and autopoiesis, very little is currently known about the physico-chemical consequences and functional role of 1D supramolecular polymerisation confined in aqueous compartments. Here, we describe the different phenomena that resulted from the chemically triggered supramolecular fibrillation of synthetic peptide amphiphiles inside water microdroplets. The confined connection of suitable dormant precursors triggered a physically autocatalysed chemical reaction that resulted in functional environmental responses such as molecular uptake, fusion and chemical exchange. These results demonstrate the potential of minimalistic 1D supramolecular polymerisation to modulate the behaviour of individual aqueous entities with their environment and within communities
Booth, R., Insua, I., Ahmed, S. et al. Supramolecular fibrillation of peptide amphiphiles induces environmental responses in aqueous droplets. Nat Commun 12, 6421 (2021). https://doi.org/10.1038/s41467-021-26681-2
2041-1723
http://hdl.handle.net/10347/30329
10.1038/s41467-021-26681-2
Self-assembly
Supramolecular polymers
Supramolecular fibrillation of peptide amphiphiles induces environmental responses in aqueous droplets
oai:minerva.usc.es:10347/170102020-01-31T09:48:41Zcom_10347_2988com_10347_2889com_10347_227com_10347_2926com_10347_2891com_10347_2888com_10347_2927col_10347_11762col_10347_15773col_10347_12292
00925njm 22002777a 4500
dc
Boga, Sonia
author
Bouzada, David
author
García Peña, Diego
author
Vázquez López, Miguel
author
Vázquez Sentís, Marco Eugenio
author
2018
Inspired by natural transcription factors (TFs), researchers have explored the potential of artificial peptides for the recognition of specific DNA sequences, developing increasingly sophisticated systems that not only display excellent DNA binding properties, but also are endowed with new properties not found in their natural counterparts. Here we review some of the developments in the field of artificial peptide‐based DNA binders, focusing on the supramolecular and molecular design aspects of such systems
Boga, S., Bouzada, D., García Peña, D., Vázquez López, M. and Vázquez, M. E. (2018), Sequence‐Specific DNA Recognition with Designed Peptides. Eur. J. Org. Chem., 2018: 249-261. doi:10.1002/ejoc.201700988
http://hdl.handle.net/10347/17010
10.1002/ejoc.201700988
1099-0690
Supramolecular chemistry
Peptides
DNA recognition
DNA binding
DNA
Metallopeptides
Chemical biology
Sequence‐Specific DNA Recognition with Designed Peptides
oai:minerva.usc.es:10347/188842023-07-10T06:16:44Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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Cobos Cabrera, Scarlet Katherine
author
Quiñoá Cabana, Emilio
author
Riguera Vega, Ricardo
author
Freire Iribarne, Félix Manuel
author
2018-08-29
A novel approach to the classical Sergeants and Soldiers effect, using chiral Sergeants and chiral Soldiers, allows control over both helical and external chirality in helical polymers. In the systems reported here, it is possible to induce the same helical sense (M or P) from either of the two enantiomers of a chiral pendant group [“chiral Soldier”, major component; i.e., (R)- or (S)-1] when it faces a single enantiomer of an appropriate “chiral Sergeant” [minor component; i.e., (S)-2]. For instance, the copolymer series poly[(R)-1r-co-(S)-2(1–r)], poly[(S)-1r-co-(S)-2(1–r)], and poly[(rac)-1r-co-(S)-2(1–r)] adopt the same P helix even though the major component shows the opposite absolute configuration. This chiral-to-chiral communication effect is transmitted by the stabilization of different conformations in each enantiomeric form of the Soldier. As a result, this groundbreaking approximation to the Sergeants and Soldiers effect allows the preparation of a single-handed helix—which depends only on the Sergeant’s configuration—with different chiralities on the helix periphery. Thus, a P helix can be decorated with the R isomer, S isomer, or even a racemic mixture of the chiral Soldier. A change in the absolute configuration of the Sergeant affords the opposite M helix, which can also be decorated with the R isomer, S isomer, or racemic mixture of the chiral Soldier
Cobos, K., Quiñoá, E., Riguera, R., & Freire, F. (2018). Chiral-to-Chiral Communication in Polymers: A Unique Approach To Control Both Helical Sense and Chirality at the Periphery. Journal Of The American Chemical Society, 140(38), 12239-12246. doi: 10.1021/jacs.8b07782
0002-7863
http://hdl.handle.net/10347/18884
10.1021/jacs.8b07782
1520-5126
Chiral-to-Chiral Communication in Polymers: A Unique Approach to Control both Helical Sense and Chirality at the Periphery
oai:minerva.usc.es:10347/306832023-07-10T06:11:52Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Gutiérrez González, Alejandro
author
Marcos Atanes, Daniel
author
Cool, Leonard G.
author
López García, Fernando José
author
Mascareñas Cid, José Luis
author
2023
Cationic cyclopentadienyl Ru(II) catalysts can efficiently promote mild intermolecular alkyne–alkene couplings in aqueous media, even in the presence of different biomolecular components, and in complex media like DMEM. The method can also be used for the derivatization of amino acids and peptides, therefore proposing a new way to label biomolecules with external tags. This C–C bond-forming reaction, based on simple alkene and alkyne reactants, can now be added to the toolbox of bioorthogonal reactions promoted by transition metal catalysts
Chem. Sci., 2023, 14, 6408
1478-6524
http://hdl.handle.net/10347/30683
10.1039/d3sc01254a
1742-2183
Ruthenium-catalyzed intermolecular alkene–alkyne couplings in biologically relevant media
oai:minerva.usc.es:10347/214082023-07-10T06:12:27Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Crisan, Daniel
author
Creese, Oliver
author
Brioso, Jose Luis
author
Montenegro García, Javier
author
Fernández Trillo, Francisco
author
2017
Here we present the synthesis and post-polymerisation modification of poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: poly(acryloyl hydrazide) was prepared from commercially available starting materials in a three step synthesis on a large scale, in good yields and high purity. Our synthetic approach included the synthesis of a Boc-protected acryloyl hydrazide, the preparation of polymers via RAFT polymerisation and the deprotection of the corresponding Boc-protected poly(acryloyl hydrazide). Post-polymerisation modification of poly(acryloyl hydrazide) was then demonstrated using a range of conditions for both hydrophilic and hydrophobic aldehydes. These experiments demonstrate the potential of poly(acryloyl hydrazide) as a scaffold in the synthesis of functional polymers, in particular those applications where in situ screening of the activity of the functionalised polymers may be required (e.g. biological applications)
Crisan, D., Creese, O., Ball, R., Brioso, J., Martyn, B., Montenegro, J., & Fernandez-Trillo, F. (2017). Poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: synthesis and post-polymerisation modification. Polymer Chemistry, 8(31), 4576-4584. doi: 10.1039/c7py00535k
http://hdl.handle.net/10347/21408
10.1039/C7PY00535K
1759-9962
Poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: synthesis and post-polymerisation modification
oai:minerva.usc.es:10347/165722023-07-10T06:12:55Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Miguel Ávila, Joan
author
Tomás Gamasa, María
author
Olmos, Andrea
author
Pérez, Pedro J.
author
Mascareñas Cid, José Luis
author
2018-01-15
The archetype reaction of “click” chemistry, namely, the copper-promoted azide–alkyne cycloaddition (CuAAC), has found an impressive number of applications in biological chemistry. However, methods for promoting intermolecular annulations of exogenous, small azides and alkynes in the complex interior of mammalian cells, are essentially unknown. Herein we demonstrate that isolated, well-defined copper(I)– tris(triazolyl) complexes featuring designed ligands can readily enter mammalian cells and promote intracellular CuAAC annulations of small, freely diffusible molecules. In addition to simplifying protocols and avoiding the addition of “non-innocent” reductants, the use of these premade copper complexes leads to more efficient processes than with the alternative, in situ made copper species prepared from Cu(II) sources, tris(triazole) ligands and sodium ascorbate. Under the reaction conditions, the well-defined copper complexes exhibit very good cell penetration properties, and do not present significant toxicities
Miguel-Ávila, J., Tomás-Gamasa, M., Olmos, A., Pérez, P., & Mascareñas, J. (2018). Discrete Cu(i) complexes for azide–alkyne annulations of small molecules inside mammalian cells. Chemical Science, 9(7), 1947-1952. http://dx.doi.org/10.1039/c7sc04643j
http://hdl.handle.net/10347/16572
10.1039/C7SC04643J
2041-6539
Discrete Cu(I) complexes for azide-alkyne annulations of small molecules inside mammalian cells
oai:minerva.usc.es:10347/168482020-10-26T09:03:15Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Fernández Ramos, Antonio
author
2013-04-04
This work presents an accurate way for calculating partition functions of strongly coupled hindered rotors in two dimensions. The two-dimensional torsional potential is generated from electronic structure calculations and fitted to Fourier series. The kinetic energy includes off-diagonal terms which are allowed to vary with the torsional angles, and these terms were also fitted to Fourier series. The resulting Hamiltonian leads to a coupled Schrödinger equation which was solved by the variational method. Therefore, the final two-dimensional non-separable (2D-NS) partition function incorporates coupling terms in both the kinetic and the potential energy. The methodology has been tested for propane, methyl formate, and a hydrogen abstraction transition state from propanone by the OH radical. How to incorporate the 2D-NS partition function in the total vibrational-rotational partition function is also discussed
Fernández-Ramos, A. (2013). Accurate treatment of two-dimensional non-separable hindered internal rotors. The Journal Of Chemical Physics, 138, 134112. doi: 10.1063/1.4798407
0031-9228
http://hdl.handle.net/10347/16848
10.1063/1.4798407
1945-0699
Accurate treatment of two-dimensional non-separable hindered internal rotors
oai:minerva.usc.es:10347/170362020-07-07T11:34:09Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Zhou, Haidong
author
Zhao, Z. Y.
author
Sun, X. F.
author
Nieto Suárez, Marina
author
Rivas Murias, Beatriz
author
Tsurkan, Vladimir
author
Deisenhofer, Joachim
author
Zapf, Vivien
author
Rivadulla, Francisco
author
2013
The magnetoelastic excitations of spin frustrated ZnCr2O4 are studied by the magnetic field dependence of the thermal conductivity k down to 50 mK. Above the first-order magnetostructural transition at TN,S≈ 12.5 K, spin fluctuations are strongly coupled to acoustic phonons, leading to a glasslike dependence of k(T), up to Θ CW. In the symmetry broken phase below TN,S, k shows a dominant magnetic contribution even at the lowest temperatures probed in this work. Application of a magnetic field above 2.5 T destabilizes the spin-bond structure, leading to a sudden increase and a nonconventional temperature dependence of the thermal conductivity. The possibility of the coexistence of gapped and gapless excitations in this magnetic phase is discussed
Zhou, H., Zhao, Z., Sun, X., Nieto Suarez, M., Rivas-Murias, B., & Tsurkan, V. et al. (2013). Low-temperature spin excitations in frustrated ZnCr2O4probed by high-field thermal conductivity. Physical Review B, 87(17). doi: 10.1103/physrevb.87.174436
2469-9950
http://hdl.handle.net/10347/17036
10.1103/PhysRevB.87.174436
2469-9969
Low-temperature spin excitations in frustrated ZnCr2O4 probed by high-field thermal conductivity
oai:minerva.usc.es:10347/213322023-07-10T06:18:11Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Schulz, Fabian
author
García Melo, Fátima
author
Kaisser, Katharina
author
Pérez Meirás, María Dolores
author
Guitián Rivera, Enrique Carlos
author
Gross, Leo
author
Peña Gil, Diego
author
2019
A route to generate cyclacenes by on-surface
synthesis is explored. We started by synthesizing two tetraepoxycyclacenes
by sequences of Diels–Alder cycloadditions.
Subsequently, these molecules were deposited onto Cu(111)
and scanning-tunneling-microscopy(STM)-based atom
manipulation was employed to dissociate the oxygen atoms.
Atomic force microscopy (AFM) with CO-functionalized tips
enabled the detailed characterization of the reaction products
and revealed that, at most, two oxygens per molecule could be
removed. Importantly, our experimental results suggest that the
generation of cyclacenes by the described route might be
possible for larger epoxycyclacenes
F. Schulz, F. García, K. Kaiser, D. Pérez, E. Guitián, L. Gross, D. Peña, Angew. Chem. Int. Ed. 2019, 58, 9038
1433-7851
http://hdl.handle.net/10347/21332
10.1002/anie.201902784
1521-3773
Atomic force microscopy
Arynes
Carbon nanobelts
Cyclacenes
Cycloadditions
Scanning tunneling microscopy
Exploring a route to cyclic acenes by on-surface synthesis
oai:minerva.usc.es:10347/197552020-01-31T14:11:03Zcom_10347_2988com_10347_2889com_10347_227com_10347_2921com_10347_2891com_10347_2888col_10347_11762col_10347_15784
00925njm 22002777a 4500
dc
Carrillo Carrión, Carolina
author
Gallego, Marta
author
Parak, Wolfgang J.
author
Carril, Mónica
author
2018
Understanding the interaction of nanoparticles with proteins and how this interaction modifies the nanoparticles’ surface is crucial before their use for biomedical applications. Since fluorinated materials are emerging as potential imaging probes and delivery vehicles, their interaction with proteins of biological interest must be studied in order to be able to predict their performance in real scenarios. It is known that fluorinated planar surfaces may repel the unspecific adsorption of proteins but little is known regarding the same process on fluorinated nanoparticles due to the scarce examples in the literature. In this context, the aim of this work is to propose a simple and fast methodology to study fluorinated nanoparticle-protein interactions based on interfacial surface tension (IFT) measurements. This technique is particularly interesting for fluorinated nanoparticles due to their increased hydrophobicity. Our study is based on the determination of IFT variations due to the interaction of quantum dots of ca. 5 nm inorganic core/shell diameter coated with fluorinated ligands (QD_F) with several proteins at the oil/water interface. Based on the results, we conclude that the presence of QD_F do not disrupt protein spontaneous film formation at the oil/water interface. Even if at very low concentrations of proteins the film formation in the presence of QD_F shows a slower rate, the final interfacial tension reached is similar to that obtained in the absence of QD_F. The differential behaviour of the studied proteins (bovine serum albumin, fibrinogen and apotransferrin) has been discussed on the basis of the adsorption affinity of each protein towards DCM/water interface and their different sizes. Additionally, it has been clearly demonstrated that the proposed methodology can serve as a complementary technique to other reported direct and indirect methods for the evaluation of nanoparticle-protein interactions at low protein concentrations
Carrillo-Carrión, C.; Gallego, M.; Parak, W.J.; Carril, M. Study of Fluorinated Quantum Dots-Protein Interactions at the Oil/Water Interface by Interfacial Surface Tension Changes. Materials 2018, 11, 750
1996-1944
http://hdl.handle.net/10347/19755
10.3390/ma11050750
Interfacial tension
Quantum dots
Fluorine
Protein-nanoparticle interaction
Protein corona
Study of Fluorinated Quantum Dots-Protein Interactions at the Oil/Water Interface by Interfacial Surface Tension Changes
oai:minerva.usc.es:10347/174102023-07-10T06:16:09Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Verdugo Leal, Felipe Ignacio
author
Villarino Palmaz, Lara
author
Durán, Juan
author
Gulías Costa, Moisés
author
Mascareñas Cid, José Luis
author
López García, Fernando
author
2018-06-04
We report a highly enantioselective [3C + 2C] intramolecular cycloaddition of alkylidenecyclopropanes (ACPs) and alkenes. The best results are obtained by using sterically demanding chiral phosphoramidite ligands derived from Vapol. Moreover, we also show that related, but less bulky, phosphoramidites can also lead to very effective [4C + 3C] cycloadditions when dienes, instead of alkenes, are used as reacting partners. The reactions provide a practical, simple, and selective access to optically active, synthetically appealing 5,5- and 5,7-bicyclic systems
Verdugo, F., Villarino, L., Durán, J., Gulías, M., Mascareñas, J., & López, F. (2018). Enantioselective Palladium-Catalyzed [3C + 2C] and [4C + 3C] Intramolecular Cycloadditions of Alkylidenecyclopropanes. ACS Catalysis, 8(7), 6100-6105. doi: 10.1021/acscatal.8b01296
2155-5435
http://hdl.handle.net/10347/17410
10.1021/acscatal.8b01296
Alkylidenecyclopropane
Asymmetric
Cycloaddition
Enantioselective
Palladium
Phosphoramidite
Enantioselective Palladium-Catalyzed [3C + 2C] and [4C + 3C] Intramolecular Cycloadditions of Alkylidenecyclopropanes
oai:minerva.usc.es:10347/169872023-07-10T06:12:23Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Prado, Gustavo
author
Veiga, Alberte X.
author
Fernández-Nieto, Fernando
author
Paleo, M. Rita
author
Sardina, F. Javier
author
2015
A two-step, stereoselective procedure for the synthesis of nine- and ten-membered carbocycles from readily available phthalates is described. A variety of dialkyl phthalates have been transformed into [6,n]-fused bicyclo systems (n = 5, 6, 7) by a dearomatization/cyclization process and then converted into cyclonona- and cyclodecadienes through a bond cleavage reaction, whereby both processes are promoted by alkaline metals in THF
Prado, G., Veiga, A., Fernández-Nieto, F., Paleo, M., & Sardina, F. (2015). A Two-Step, Stereoselective Synthesis of Nine- and Ten-Membered Carbocycles from Phthalates. Org. Lett., 17(9), 2054-2057. doi: 10.1021/acs.orglett.5b00552
1523-7060
http://hdl.handle.net/10347/16987
10.1021/acs.orglett.5b00552
1523-7052
A Two-Step, Stereoselective Synthesis of Nine- and Ten-Membered Carbocycles from Phthalates
oai:minerva.usc.es:10347/273752022-01-21T03:02:28Zcom_10347_2897com_10347_2890com_10347_2888com_10347_227com_10347_2988com_10347_2889com_10347_17063com_10347_15468com_10347_2925com_10347_2891col_10347_12277col_10347_11762col_10347_17064col_10347_9937
00925njm 22002777a 4500
dc
Illodo, Sara
author
Pérez González, Cibrán
author
Barcia, Ramiro
author
Rodriguez-Prieto, Flor
author
Al-Soufi, Wajih
author
Novo Rodríguez, Mercedes
author
2022
Guanine quadruplexes (G4s) are highly polymorphic four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of the first G4 structures within mitochondrial DNA has led to a small revolution in the field. In particular, the G-rich conserved sequence block II (CSB II) can form different types of G4s that are thought to play a crucial role in replication. In this study, we decipher the most relevant G4 structures that can be formed within CSB II: RNA G4 at the RNA transcript, DNA G4 within the non-transcribed strand and DNA:RNA hybrid between the RNA transcript and the non-transcribed strand. We show that the more abundant, but unexplored, G6AG7 (37%) and G6AG8 (35%) sequences in CSB II yield more stable G4s than the less profuse G5AG7 sequence. Moreover, the existence of a guanine located 1 bp upstream promotes G4 formation. In all cases, parallel G4s are formed, but their topology changes from a less ordered to a highly ordered G4 when adding small amounts of potassium or sodium cations. Circular dichroism was used due to discriminate different conformations and topologies of nucleic acids and was complemented with gel electrophoresis and fluorescence spectroscopy studies
Illodo, S.; Pérez-González, C.; Barcia, R.; Rodríguez-Prieto, F.; Al-Soufi, W.; Novo, M. Spectroscopic Characterization of Mitochondrial G-Quadruplexes. Int. J. Mol. Sci. 2022, 23, 925. https://doi.org/10.3390/ ijms23020925
1422-0067
http://hdl.handle.net/10347/27375
10.3390/ijms23020925
DNA quadruplexes
G-quadruplex CD and fluorescence spectroscopy
G-quadruplex structure
Spectroscopic characterization of mitochondrial G-quadruplexes
oai:minerva.usc.es:10347/223272020-05-16T02:00:53Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Arrigo, Rossella
author
Antonioli, Diego
author
Lazzari, Massimo
author
Gianotti, Valentina
author
Laus, Michele
author
Montanaro, Laura
author
Malucelli, Giulio
author
2018
Polyethylene glycol-based nanocomposites containing an organo-modified hydrotalcite with loadings ranging from 0.5 to 5 wt.% were prepared by melt mixing performed just above the melting point of the polymer matrix. In these conditions, the dispersion of the nanofiller within the polymer matrix was quite homogeneous as revealed by TEM analyses. The effect of various thermal treatments and filler loadings was thoroughly investigated by means of rheological, morphological and gas chromatography-mass spectrometry, hyphenated to thermogravimetry analysis tests. Unfilled polyethylene glycol exhibited a continuous decrease in complex viscosity upon heating. In contrast, the complex viscosity of nanocomposites containing nanofiller loadings higher than 1 wt.% showed first a decrease, followed by an increase in the complex viscosity as the temperature increases, exhibiting a minimum between 130 and 140 °C. Annealing at 180 °C for different times further increased the viscosity of the system. This unusual behavior was explained by the occurrence of grafting reactions between the –OH terminal groups of the polyethylene glycol chains and the hydroxyl groups of the organo-modified filler, thus remarkably affecting the relaxation dynamics of the system
Arrigo, R.; Antonioli, D.; Lazzari, M.; Gianotti, V.; Laus, M.; Montanaro, L.; Malucelli, G. Relaxation Dynamics in Polyethylene Glycol/Modified Hydrotalcite Nanocomposites. Polymers 2018, 10, 1182
http://hdl.handle.net/10347/22327
10.3390/polym10111182
2073-4360
Rheological behavior
Polyethylene glycol
Organo-modified hydrotalcite
Grafting reactions
Annealing
Relaxation Dynamics in Polyethylene Glycol/Modified Hydrotalcite Nanocomposites
oai:minerva.usc.es:10347/169322023-07-10T06:12:42Zcom_10347_2897com_10347_2890com_10347_2888com_10347_227com_10347_2988com_10347_2889col_10347_12277col_10347_11762
00925njm 22002777a 4500
dc
Blanco Rodríguez, Beatriz
author
Sedes, Antía
author
Peón López, Antonio
author
Otero Casas, José Manuel
author
Raaij, Mark J. van
author
Thompson, Paul
author
Hawkins, Alastair R.
author
González Bello, Concepción
author
2014
Structural and computational studies to explore the WAT1 binding pocket in the structure-based design of inhibitors against the type II dehydroquinase (DHQ2) enzyme are reported. The crystal structures of DHQ2 from M. tuberculosis in complex with four of the reported compounds are described. The electrostatic interaction observed between the guanidinium group of the essential arginine and the carboxylate group of one of the inhibitors in the reported crystal structures supports the recently suggested role of this arginine as the residue that triggers the release of the product from the active site. The results of the structural and molecular dynamics simulation studies revealed that the inhibitory potency is favored by promoting interactions with WAT1 and the residues located within this pocket and, more importantly, by avoiding situations where the ligands occupy the WAT1 binding pocket. The new insights can be used to advantage in the structure-based design of inhibitors
Blanco, B., Sedes, A., Peón, A., Otero, J., van Raaij, M., & Thompson, P. et al. (2014). Exploring the Water-Binding Pocket of the Type II Dehydroquinase Enzyme in the Structure-Based Design of Inhibitors. Journal Of Medicinal Chemistry, 57(8), 3494-3510. doi: 10.1021/jm500175z
0022-2623
http://hdl.handle.net/10347/16932
10.1021/jm500175z
1520-4804
Exploring the Water-Binding Pocket of the Type II Dehydroquinase Enzyme in the Structure-Based Design of Inhibitors
oai:minerva.usc.es:10347/233182023-07-10T06:13:02Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Panighel, Mirco
author
Quiroga Fernández, Sabela
author
Brandimarte, Pedro
author
Moreno, Cesar
author
García Lekue, Aran
author
Vilas Varela, Manuel
author
Rey Vieites, Dulce María
author
Sauthier, Guillaume
author
Ceballos, Gustavo
author
Peña Gil, Diego
author
Mugarza, Aitor
author
2020
The on-surface synthesis of edge-functionalized graphene nanoribbons (GNRs) is challenged by the stability of the functional groups throughout the thermal reaction steps of the synthetic pathway. Edge fluorination is a particularly critical case in which the interaction with the catalytic substrate and intermediate products can induce the complete cleavage of the otherwise strong C–F bonds before the formation of the GNR. Here, we demonstrate how a rational design of the precursor can stabilize the functional group, enabling the synthesis of edge-fluorinated GNRs. The survival of the functionalization is demonstrated by tracking the structural and chemical transformations occurring at each reaction step with complementary X-ray photoelectron spectroscopy and scanning tunneling microscopy measurements. In contrast to previous attempts, we find that the C–F bond survives the cyclodehydrogenation of the intermediate polymers, leaving a thermal window where GNRs withhold more than 80% of the fluorine atoms. We attribute this enhanced stability of the C–F bond to the particular structure of our precursor, which prevents the cleavage of the C–F bond by avoiding interaction with the residual hydrogen originated in the cyclodehydrogenation. This structural protection of the linking bond could be implemented in the synthesis of other sp2-functionalized GNRs
ACS Nano 2020, 14, 9, 11120–11129
1936-0851
http://hdl.handle.net/10347/23318
10.1021/acsnano.0c01837
1936-086X
Precursors
Bond cleavage
Energy
X-ray photoelectron spectroscopy
Scanning tunneling microscopy
Stabilizing Edge Fluorination in Graphene Nanoribbons
oai:minerva.usc.es:10347/160162023-07-10T06:12:04Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Rodríguez Villar, Jéssica
author
Mosquera Mosquera, Jesús
author
García Fandiño, Rebeca
author
Vázquez Sentís, Marco Eugenio
author
Mascareñas Cid, José Luis
author
2016-02-05
We report the rational design of a DNA-binding peptide construct composed of the DNA-contacting regions of two transcription factors (GCN4 and GAGA) linked through an AT-hook DNA anchor. The resulting chimera, which represents a new, non-natural DNA binding motif, binds with high affinity and selectivity to a long composite sequence of 13 base pairs (TCAT-AATT-GAGAG)
J. Rodríguez, J. Mosquera, R. García-Fandiño, M. E. Vázquez and J. L. Mascareñas, Chem. Sci., 2016, 7, 3298–3303
2041-6539
http://hdl.handle.net/10347/16016
10.1039/c6sc00045b
A designed DNA binding motif that recognizes extended sites and spans two adjacent major grooves
oai:minerva.usc.es:10347/184772023-07-10T06:16:40Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Villarino Palmaz, Lara
author
García Fandiño, Rebeca
author
López García, Fernando
author
Mascareñas Cid, José Luis
author
2012
A practical protocol for the hydroalkynylation of enones using Pd catalysis is reported. The reaction proceeds efficiently with a variety of alkynes as well as with several cyclic and acyclic enones, providing synthetically relevant β-alkynyl ketones in good to excellent yields
Villarino, L., García-Fandiño, R., López, F., & Mascareñas, J. (2012). Palladium-Catalyzed Conjugate Addition of Terminal Alkynes to Enones. Org. Lett., 14, 12, 2996-2999. DOI: 10.1021/ol300988n
1523-7060
http://hdl.handle.net/10347/18477
10.1021/ol300988n
1523-7052
Palladium-Catalyzed Conjugate Addition of Terminal Alkynes to Enones
oai:minerva.usc.es:10347/149122023-07-10T06:11:56Zcom_10347_2897com_10347_2890com_10347_2888com_10347_227com_10347_2988com_10347_2889com_10347_2927com_10347_2891col_10347_12277col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Martínez Costas, José Manuel
author
Fernández Trillo, Francisco
author
Montenegro García, Javier
author
Granja Guillán, Juan Ramón
author
Priegue Caamaño, Juan Manuel
author
Crisan, Daniel
author
2016-04-21
A new method is reported herein for screening the biological activity of functional polymers across a consistent degree of polymerization and in situ, that is, under aqueous conditions and without purification/isolation of candidate polymers. In brief, the chemical functionality of a poly(acryloyl hydrazide) scaffold was activated under aqueous conditions using readily available aldehydes to obtain amphiphilic polymers. The transport activity of the resulting polymers can be evaluated in situ using model membranes and living cells without the need for tedious isolation and purification steps. This technology allowed the rapid identification of a supramolecular polymeric vector with excellent efficiency and reproducibility for the delivery of siRNA into human cells (HeLa-EGFP). The reported method constitutes a blueprint for the high-throughput screening and future discovery of new polymeric functional materials with important biological applications
J. M. Priegue, D. N. Crisan, J. Martínez-Costas, J. R. Granja, F. Fernandez-Trillo, J. Montenegro, Angew. Chem. Int. Ed. 2016, 55, 7492
1433-7851
http://hdl.handle.net/10347/14912
10.1002/anie.201601441
1521-3773
Lipid bilayer membranes
Polymers
siRNA delivery
Supramolecular chemistry
Vesicles
In situ functionalized polymers for siRNA delivery
oai:minerva.usc.es:10347/169842023-07-10T06:12:16Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Domínguez, José L.
author
Fernández-Nieto, Fernando
author
Brea Floriani, José Manuel
author
CATTO, Marco
author
Paleo, M. Rita
author
Porto, Silvia
author
Sardina, F. Javier
author
Castro, Marian
author
PISANI, Leonardo
author
Carotti, Angelo
author
Soto-Otero, Ramón
author
Méndez-Álvarez, Estefanía
author
Villaverde Cameron-Walker, María del Carmen
author
Sussman, Fredy Salomon
author
2016-07-22
This work is part of our ongoing research in the discovery of multitarget therapeutic agents for Alzheimer's disease (AD). A literature screening, based on our recently proposed pharmacophore, led to the identification of 8‐aminomethyl‐7‐hydroxy‐4‐methyl coumarins as potential multitarget leads for AD. The results of a computer‐assisted protocol developed by us to validate multitarget hits for AD indicated that our coumarin candidates were viable leads only for AChE inhibition as later validated by biological assays. The results of BChE binding and propidium displacement assays indicate that our first generation compounds bind to the PAS site in AChE. We designed new generations of coumarin derivatives with a longer substituent at position 8 aimed at leads with more efficient interaction at the catalytic anionic site (CAS). Inhibition data and docking simulations indicated that an anilino‐capping group reached the CAS region of AChE and determined also a higher inhibitory potency towards BChE. The best compound obtained, with a N‐benzylpiperidine fragment, displayed sub‐micromolar affinity for AChE, affinity for BChE, and precluded Aβ‐amyloid aggregation with a potency similar to that of 9,10‐anthraquinone, making it a multitarget lead viable for further improvement
Domínguez, J., Fernández-Nieto, F., Brea, J., Catto, M., Paleo, M., & Porto, S. et al. (2016). 8-Aminomethyl-7-hydroxy-4-methylcoumarins as Multitarget Leads for Alzheimer's Disease. Chemistryselect, 1(11), 2742-2749. doi: 10.1002/slct.201600735
http://hdl.handle.net/10347/16984
10.1002/slct.201600735
2365-6549
Alzheimer's disease
8-aminomethyl-7-hydroxy-4-methylcoumarins
Cholinesterases inhibition
Computational chemistry
Drug design
Multitarget leads
8‐Aminomethyl‐7‐hydroxy‐4‐methylcoumarins as Multitarget Leads for Alzheimer's Disease
oai:minerva.usc.es:10347/232092023-07-10T06:21:40Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Verdugo Leal, Felipe Ignacio
author
Concepción Vicente, Eduardo da
author
Rodiño Balboa, Ricardo
author
Calvelo Souto, Martín
author
Mascareñas Cid, José Luis
author
López García, Fernando
author
2020
A Pd catalyst made from a Pd(0) source and a bulky biaryl phosphine ligand promotes highly efficient intramolecular (3 + 2) heterocycloadditions between alkylidenecyclopropanes (ACPs) and carbonyls. The annulations provide a straightforward access to fused polycyclic systems featuring β-methylene tetrahydrofuran moieties. DFT data support a pallada–ene process and shed light on the critical role of hemilabile interactions between the Pd center and the bulky biaryl phosphine. Significantly, these Pd(0) catalysts are also effective for promoting intermolecular formal cycloadditions between ACPs and trifluoromethyl ketones, thus providing for a direct entry to chiral tetrahydrofuran moieties (THFs) bearing trifluoromethyl–substituted carbons
ACS Catal. 2020, 10, 14, 7710–7718
http://hdl.handle.net/10347/23209
10.1021/acscatal.0c01827
2155-5435
Palladium
Hydrocarbons
Cyclization
Ketones
Catalysts
Alkylidenecyclopropane
Cycloaddition
Pd-Catalyzed (3 + 2) Heterocycloadditions between Alkylidenecyclopropanes and Carbonyls: Straightforward Assembly of Highly Substituted Tetrahydrofurans
oai:minerva.usc.es:10347/302602023-07-10T06:11:14Zcom_10347_2988com_10347_2889com_10347_227com_10347_2921com_10347_2891com_10347_2888com_10347_2926col_10347_11762col_10347_15784col_10347_15773
00925njm 22002777a 4500
dc
Soprano, Enrica
author
Polo Tobajas, Ester
author
Pelaz García, Beatriz
author
Pino González de la Higuera, Pablo Alfonso del
author
2022
Nanoparticles have now long demonstrated capabilities that make them attractive to use in biology and medicine. Some of them, such as lipid nanoparticles (SARS-CoV-2 vaccines) or metallic nanoparticles (contrast agents) are already approved for their use in the clinic. However, considering the constantly growing body of different formulations and the huge research around nanomaterials the number of candidates reaching clinical trials or being commercialized is minimal. The reasons behind being related to the “synthetic” and “foreign” character of their surface. Typically, nanomaterials aiming to develop a function or deliver a cargo locally, fail by showing strong off-target accumulation and generation of adverse responses, which is connected to their strong recognition by immune phagocytes primarily. Therefore, rendering in negligible numbers of nanoparticles developing their intended function. While a wide range of coatings has been applied to avoid certain interactions with the surrounding milieu, the issues remained. Taking advantage of the natural cell membranes, in an approach that resembles a cell transfer, the use of cell-derived surfaces has risen as an alternative to artificial coatings or encapsulation methods. Biomimetic technologies are based on the use of isolated natural components to provide autologous properties to the nanoparticle or cargo being encapsulated, thus, improving their therapeutic behavior. The main goal is to replicate the (bio)-physical properties and functionalities of the source cell and tissue, not only providing a stealthy character to the core but also taking advantage of homotypic properties, that could prove relevant for targeted strategies. Such biomimetic formulations have the potential to overcome the main issues of approaches to provide specific features and identities synthetically. In this review, we provide insight into the challenges of nano-biointerfaces for drug delivery; and the main applications of biomimetic materials derived from specific cell types, focusing on the unique strengths of the fabrication of novel nanotherapeutics in cancer therapy
Soprano, E., Polo, E., Pelaz, B. et al. Biomimetic cell-derived nanocarriers in cancer research. J Nanobiotechnol 20, 538 (2022). https://doi.org/10.1186/s12951-022-01748-4
1477-3155
http://hdl.handle.net/10347/30260
10.1186/s12951-022-01748-4
Biomimetic nanocarrier
Drug delivery
Intracellular delivery
Cancer therapy
Cell-membrane coating
Nanoparticles
Biomimetic cell-derived nanocarriers in cancer research
oai:minerva.usc.es:10347/213142023-07-10T06:17:58Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Li, Jingcheng
author
Sanz, Sofia
author
Choi, Deung Jang
author
Corso, Martina
author
Peña Gil, Diego
author
Frederiksen, Thomas
author
Pascual, Jose Ignacio
author
2019
Turning graphene magnetic is a promising challenge to make it an active material for spintronics. Predictions state that graphene structures with specific shapes can spontaneously develop magnetism driven by Coulomb repulsion of π-electrons, but its experimental verification is demanding. Here, we report on the observation and manipulation of individual magnetic moments in graphene open-shell nanostructures on a gold surface. Using scanning tunneling spectroscopy, we detect the presence of single electron spins localized around certain zigzag sites of the carbon backbone via the Kondo effect. We find near-by spins coupled into a singlet ground state and quantify their exchange interaction via singlet-triplet inelastic electron excitations. Theoretical simulations picture how electron correlations result in spin-polarized radical states with the experimentally observed spatial distributions. Extra hydrogen atoms bound to radical sites quench their magnetic moment and switch the spin of the nanostructure in half-integer amounts. Our work demonstrates the intrinsic π-paramagnetism of graphene nanostructures
Li, J., Sanz, S., Corso, M. et al. Single spin localization and manipulation in graphene open-shell nanostructures. Nat Commun 10, 200 (2019). https://doi.org/10.1038/s41467-018-08060-6
http://hdl.handle.net/10347/21314
10.1038/s41467-018-08060-6
2041-1723
Graphene
Nanostructures
Single spin localization and manipulation in graphene open-shell nanostructures
oai:minerva.usc.es:10347/170282023-07-10T06:12:03Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Iglesias, L.
author
Sarantopoulos, Alexandros
author
Magén, Cesar
author
Rivadulla, Francisco
author
2017
We report the enthalpy of oxygen vacancy formation in thin films of electron-doped
SrTiO
3
, under different degrees of epitaxial stress. We demonstrate that both compressive and tensile strain decrease this energy at a very similar rate and promote the formation of stable doubly ionized oxygen vacancies. Moreover, we also show that unintentional cationic vacancies introduced under typical growth conditions, produce a characteristic rotation pattern of TiO6 octahedra. The local concentration of oxygen vacancies can be modulated by an electric field with an AFM tip, changing not only the local electrical potential but also producing a nonvolatile mechanical response whose sign (up/down) can be reversed by the electric field
Iglesias, L., Sarantopoulos, A., Magén, C., & Rivadulla, F. (2017). Oxygen vacancies in strained SrTiO3 thin films: Formation enthalpy and manipulation. Physical Review B, 95(16). doi: 10.1103/physrevb.95.165138
2469-9950
http://hdl.handle.net/10347/17028
10.1103/PhysRevB.95.165138
2469-9969
Conductivity
Vacancies
Atomic force microscopy
Condensed Matter
Materials Physics
Oxygen vacancies in strained SrTiO 3 thin films: Formation enthalpy and manipulation
oai:minerva.usc.es:10347/248482023-07-10T06:16:23Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Destito, Paolo
author
Vidal Vides, Cristian
author
López García, Fernando
author
Mascareñas Cid, José Luis
author
2021
During the last decade, there has been a tremendous interest for developing non‐natural biocompatible transformations in biologically relevant media. Among the different encountered strategies, the use of transition metal complexes offers unique possibilities due to their high transformative power. However, translating the potential of metal catalysts to biological settings, including living cells or small‐animal models such as mice or zebrafish, poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Herein, we describe the most relevant advances in this direction, with a particular emphasis on the systems’ structure, their mode of action and the mechanistic bases of each transformation. Thus, the key challenges from an organometallic perspective might be more easily identified
Destito, P.; Vidal, C.; and López, F.; Mascareñas, J. L. (2021), Transition Metal- Promoted Reactions in Aqueous Media and Biological Settings. Chem. Eur. J., 27: 4789-4816. doi: 10.1002/chem.202003927
http://hdl.handle.net/10347/24848
10.1002/chem.202003927
1521-3765
Aqueous catalysis
Biocatalysis
Biological chemistry
Cellular chemistry
Organometallic catalysis
Transition Metal‐Promoted Reactions in Aqueous Media and Biological Settings
oai:minerva.usc.es:10347/292342023-07-10T06:11:14Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Chaves Pouso, Andrea
author
Álvarez Constantino, Andrés Manuel
author
Fañanás Mastral, Martín
author
2022
A highly chemo-, regio-, enantio- and diastereoselective coupling of terminal alkynes, bis(pinacolato)diboron and allylic gem-dichlorides is reported. The method uses a chiral NHC−Cu catalyst which generates, in a single step, synthetically versatile chiral skipped dienes bearing a Z-alkenyl chloride, a trisubstituted E-alkenyl boronate and a bis-allylic stereocenter. Allylic gem-dichlorides are shown to be efficient substrates for catalytic asymmetric allylboration of alkynes. The method employs a chiral NHC−Cu catalyst capable of generating in a single step chiral skipped dienes bearing a Z-alkenyl chloride, a trisubstituted E-alkenyl boronate and a bis-allylic stereocenter with excellent levels of chemo-, regio- enantio- and diastereoselectivity. This high degree of functionalization makes these products versatile building blocks as illustrated with the synthesis of several optically active compounds. DFT calculations support the key presence of a metal cation bridge ligand–substrate interaction and account for the stereoselectivity outcome
Angew. Chem.Int. Ed.2022,61,e202117696
http://hdl.handle.net/10347/29234
10.1002/anie.202117696
0570-0833
Asymmetric catalysis
Carboboration
Copper
gem-Dichlorides
Skipped Dienes
Enantio- and Diastereoselective Copper-Catalyzed Allylboration of Alkynes with Allylic gem-Dichlorides
oai:minerva.usc.es:10347/197572020-04-16T19:20:01Zcom_10347_2988com_10347_2889com_10347_227com_10347_2921com_10347_2891com_10347_2888col_10347_11762col_10347_15784
00925njm 22002777a 4500
dc
Comas, Laura
author
Polo Tobajas, Ester
author
Domingo, M. Pilar
author
Hernández, Yulán
author
Arias, Maykel
author
Esteban, Patricia
author
Martínez-Lostao, Luis
author
Pardo, Julián
author
Martínez de la Fuente, Jesús
author
Gálvez, Eva M.
author
2019
Gliotoxin (GT), a secondary metabolite produced by Aspergillus molds, has been proposed as a potential anti-tumor agent. Here we have developed a nanoparticle approach to enhance delivery of GT in tumor cells and establish a basis for its potential use as therapeutical drug. GT bound to magnetic nanoparticles (MNPs) retained a high anti-tumor activity, correlating with efficient intracellular delivery, which was increased in the presence of glucose. Our results show that the attachment of GT to MNPs by covalent bonding enhances intracellular GT delivery without affecting its biological activity. This finding represents the first step to use this potent anti-tumor agent in the treatment of cancer
Comas, L.; Polo, E.; Domingo, M.P.; Hernández, Y.; Arias, M.; Esteban, P.; Martínez-Lostao, L.; Pardo, J.; Martínez de la Fuente, J.; Gálvez, E.M. Intracellular Delivery of Biologically-Active Fungal Metabolite Gliotoxin Using Magnetic Nanoparticles. Materials 2019, 12, 1092
1996-1944
http://hdl.handle.net/10347/19757
10.3390/ma12071092
Magnetic nanoparticles
Gliotoxin
Therapeutic
Drug delivery
Cancer cells
Intracellular Delivery of Biologically-Active Fungal Metabolite Gliotoxin Using Magnetic Nanoparticles
oai:minerva.usc.es:10347/204332023-07-10T06:17:17Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Langenberg Pérez, Eric
author
Saha, Dipanjan
author
Holtz, Megan E.
author
Wang, Jian-Jun
author
Bugallo Ferrón, David
author
Ferreiro Vila, Elías
author
Paik, Hanjong
author
Hanke, Isabelle
author
Ganschow, Steffen
author
Muller, David A.
author
Chen, Long-Qing
author
Catalan, Gustau
author
Domingo, Neus
author
Malen, Jonathan
author
Schlom, Darrell G.
author
Rivadulla Fernández, José Francisco
author
2019
Achieving efficient spatial modulation of phonon transmission is an essential step on the path to phononic circuits using “phonon currents”. With their intrinsic and reconfigurable interfaces, domain walls (DWs), ferroelectrics are alluring candidates to be harnessed as dynamic heat modulators. This paper reports the thermal conductivity of single-crystal PbTiO3 thin films over a wide variety of epitaxial-strain-engineered ferroelectric domain configurations. The phonon transport is proved to be strongly affected by the density and type of DWs, achieving a 61% reduction of the room-temperature thermal conductivity compared to the single-domain scenario. The thermal resistance across the ferroelectric DWs is obtained, revealing a very high value (≈5.0 × 10–9 K m2 W–1), comparable to grain boundaries in oxides, explaining the strong modulation of the thermal conductivity in PbTiO3. This low thermal conductance of the DWs is ascribed to the structural mismatch and polarization gradient found between the different types of domains in the PbTiO3 films, resulting in a structural inhomogeneity that extends several unit cells around the DWs. These findings demonstrate the potential of ferroelectric DWs as efficient regulators of heat flow in one single material, overcoming the complexity of multilayers systems and the uncontrolled distribution of grain boundaries, paving the way for applications in phononics
Nano Lett. 2019, 19, 11, 7901-7907
1530-6984
http://hdl.handle.net/10347/20433
10.1021/acs.nanolett.9b02991
1530-6992
Epitaxial strain engineering
Domain walls
Ferroelectrics
Thermal conductivity
Thin films
Phononics
Ferroelectric Domain Walls in PbTiO3 Are Effective Regulators of Heat Flow at Room Temperature
oai:minerva.usc.es:10347/267962023-07-10T06:11:47Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Lence Quintana, Emilio José
author
González Bello, Concepción
author
2021
The use of β-lactamase inhibitors in combination with β-lactam antibiotics is an emerging area in drug discovery. This strategy allows the restoration of the therapeutic efficacy of these antibiotics in clinical use against multiresistant bacteria. These pathogens are drug resistant because they express β-lactamase enzymes, which prevent the antibiotic therapeutic action by catalyzing the hydrolysis of the β-lactam ring. These enzymes are quite diverse in both their structural architecture and hydrolytic capability, as well as in the mechanism of action. The ever-increasing emergence of pathogens that are capable of coproducing different types of β-lactamases has triggered the search for ultrabroad-spectrum inhibitors capable of deactivating both serine- and metallo-β-lactamases. A recent breakthrough in this long-pursued and unmet need is the discovery of bicyclic boronate inhibitors, specifically taniborbactam, VNRX-7145, and QPX7728, which are currently under clinical development in combination with cefepime, ceftibuten, and QPX2014, respectively. The present article highlights the therapeutic potential of these inhibitors and their spectrum of efficacy is compared with those of other β-lactam/β-lactamase inhibitor combinations recently approved by the food and drug administration. The molecular basis of the ultrabroad-spectrum of activity of boron-based inhibitors is also discussed, on the basis of the available crystal structures and the results of computational studies
Adv. Therap. 2021, 4: 2000246. https://doi.org/10.1002/adtp.202000246
http://hdl.handle.net/10347/26796
10.1002/adtp.202000246
2366-3987
Antibiotic adjuvants
Boron-based inhibitors
Metallo-β-lactamases
Resistance breakers
Serine-β-lactamases
Bicyclic Boronate β-Lactamase Inhibitors: The Present Hope against Deadly Bacterial Pathogens
oai:minerva.usc.es:10347/306202023-07-10T06:11:21Zcom_10347_2988com_10347_2889com_10347_227com_10347_2919com_10347_2891com_10347_2888com_10347_2927col_10347_11762col_10347_10699col_10347_12292
00925njm 22002777a 4500
dc
Cabezón Vizoso, Alfonso
author
Calvelo Souto, Martín
author
Granja Guillán, Juan Ramón
author
Piñeiro Guillén, Ángel
author
García Fandiño, Rebeca
author
2023
Cyclic peptides (CPs) formed by alternation of D- and L-amino acids (D,L-CPs) can self-assemble into nanotubes (SCPNs) by parallel or/and antiparallel stacking. Different applications have been attributed to these nanotubes, including the disruption of lipid bilayers of specific compositions and the selective transport of ions throughout membranes. Molecular dynamics (MD) simulations have significantly contributed to understand the interaction between CPs, including the structural, dynamic and transport properties of their supramolecular aggregates. The high computational cost of atomic resolution forcefields makes them impractical for simulating the self-assembly of macromolecules, so coarse-grained (CG) models might represent a more feasible solution for this purpose. However, general CG models used for the simulation of biomolecules such as the MARTINI forcefield do not explicitly consider the non-covalent interactions leading to the formation of secondary structure patterns in proteins. This becomes particularly important in the case of CPs due to the D- and L-chirality alternation in their sequence, leading to opposite orientations of the backbone polar groups on both sides of the cyclic ring plane. In order to overcome this limitation, we have extended the MARTINI forcefield to introduce chirality in each residue of the CPs. The new parametrization, which we have called MA(R/S)TINI, reproduces the expected self-assembly patterns for several CP sequences in the presence of different membrane models, explicitly considering the chirality of the CPs and with no significant extra computational cost. Our simulations provide new mechanistic information of how these systems self-assemble in presence of different lipid scenarios, showing that the CP-CP and CP-membrane interactions are sensitive to the peptide sequence chirality. This opens the door to design new bioactive CPs based on CG-MD simulations. A web-based tool for the automatic parameterization of new CP sequences using MA(R/S)TINI, among other functionalities, is under construction (see http://cyclopep.com)
Journal of Colloid and Interface Science 642 (2023) 84-99
http://hdl.handle.net/10347/30620
10.1016/j.jcis.2023.03.101
0021-9797
Cyclic peptides
Coarse-grained molecular dynamics simulations
Martini forcefield
Lipid bilayers
Uncovering the mechanisms of cyclic peptide self-assembly in membranes with the chirality-aware MA(R/S)TINI forcefield
oai:minerva.usc.es:10347/220342023-07-10T06:18:24Zcom_10347_2897com_10347_2890com_10347_2888com_10347_227com_10347_2988com_10347_2889col_10347_12277col_10347_11762
00925njm 22002777a 4500
dc
Schonherr, R.
author
Klinge, M.
author
Rudolph, J. M.
author
Fita, K.
author
Rehders, D.
author
Lubber, F.
author
Schneegans, S.
author
Majoul, I. V.
author
Duszenko, M.
author
Betzel, C.
author
Brandariz Núñez, Alberto
author
Martínez Costas, José Manuel
author
Duden, R.
author
Redecke, L.
author
2015
X-ray crystallography requires sufficiently large crystals to obtain structural insights at atomic resolution, routinely obtained in vitro by time-consuming screening. Recently, successful data collection was reported from protein microcrystals grown within living cells using highly brilliant free-electron laser and third-generation synchrotron radiation. Here, we analyzed in vivo crystal growth of firefly luciferase and Green Fluorescent Protein-tagged reovirus μNS by live-cell imaging, showing that dimensions of living cells did not limit crystal size. The crystallization process is highly dynamic and occurs in different cellular compartments. In vivo protein crystallization offers exciting new possibilities for proteins that do not form crystals in vitro.
Schonherr, R., Klinge, M., Rudolph, J.M. et al. (2015). Real-time investigation of dynamic protein crystallization in living cells, "Structural Dynamics" 2, 041712
2329-7778
http://hdl.handle.net/10347/22034
10.1063/1.4921591
Real-time investigation of dynamic protein crystallization in living cells
oai:minerva.usc.es:10347/166922023-07-10T06:12:06Zcom_10347_2988com_10347_2889com_10347_227com_10347_2926com_10347_2891com_10347_2888col_10347_11762col_10347_15773
00925njm 22002777a 4500
dc
Giménez López, María del Carmen
author
Clemente León, Miguel
author
Giménez-Saiz, Carlos
author
2018-05-02
M. D. C. Gimenez Lopez, M. Clemente Leon and C. Giménez-Saiz, Dalton Trans., 2018, DOI: 10.1039/C8DT01269E
1477-9226
http://hdl.handle.net/10347/16692
10.1039/C8DT01269E
1477-9234
Unravelling the spin-state of solvated [Fe(bpp)2]
2+ spin-crossover complexes:
structure-function relationship
oai:minerva.usc.es:10347/243132023-07-10T06:21:34Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Priegue Caamaño, Juan Manuel
author
Lostalé Seijo, Irene
author
Crisan, Daniel
author
Granja Guillán, Juan Ramón
author
Fernández Trillo, Francisco
author
Montenegro García, Javier
author
2018
The recent advances in genetic engineering demand the development of conceptually new methods to prepare and identify efficient vectors for the intracellular delivery of different nucleotide payloads ranging from short single-stranded oligonucleotides to larger plasmid double-stranded circular DNAs. Although many challenges still have to be overcome, polymers hold great potential for intracellular nucleotide delivery and gene therapy. We here develop and apply the postpolymerization modification of polyhydrazide scaffolds, with different degree of polymerization, for the preparation of amphiphilic polymeric vehicles for the intracellular delivery of a circular plasmid DNA. The hydrazone formation reactions with a mixture of cationic and hydrophobic aldehydes proceed in physiologically compatible aqueous conditions, and the resulting amphiphilic polyhydrazones are directly combined with the biological cargo without any purification step. This methodology allowed the preparation of stable polyplexes with a suitable size and zeta potential to achieve an efficient encapsulation and intracellular delivery of the DNA cargo. Simple formulations that performed with efficiencies and cell viabilities comparable to the current gold standard were identified. Furthermore, the internalization mechanism was studied via internalization experiments in the presence of endocytic inhibitors and fluorescence microscopy. The results reported here confirmed that the polyhydrazone functionalization is a suitable strategy for the screening and identification of customized polymeric vehicles for the delivery of different nucleotide cargos
Biomacromolecules 2018, 19, 7, 2638–2649
1525-7797
http://hdl.handle.net/10347/24313
10.1021/acs.biomac.8b00252
1526-4602
Aldehydes
Genetics
Fluorescence
Gene delivery
Polymers
Different-Length Hydrazone Activated Polymers for Plasmid DNA Condensation and Cellular Transfection
oai:minerva.usc.es:10347/119682023-07-10T06:16:24Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Mosquera Mosquera, Jesús
author
Sánchez López, Mateo Isidro
author
Vázquez Sentís, Marco Eugenio
author
Mascareñas Cid, José Luis
author
2014-07-28
We report a photolabile biselectrophilic Ru(II) complex that can be used for homo- or heterodimerization of cysteine-containing peptides. The resulting dimers can be efficiently disassembled by long-wavelength light. As proof-of-concept, we describe the preparation of homo- and heterodimeric bZIP peptides whose DNA-binding properties can be turned off using visible light
Mosquera, J., Sánchez, M. I., Vázquez, M. E. and Mascareñas, J. L. (2014), Ruthenium bipyridyl complexes as photocleavable dimerizers: deactivation of DNA-binding peptides using visible light. Chem. Commun., 50, 10975-10978 [doi: 10.1039/C4CC04512B]
1364-548X
http://hdl.handle.net/10347/11968
10.1039/c4cc04512b
Ruthenium bipyridyl complexes as photocleavable dimerizers: deactivation of DNA-binding peptides using visible light
oai:minerva.usc.es:10347/243102023-07-10T06:21:34Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Matos, Maria João Correia Pinto Carvalho de
author
Oliveira, Bruno L.
author
Martínez Saéz, Nuria
author
Guerreiro, Ana
author
Cal, Pedro M.S.D.
author
Bertoldo, Jean Borges
author
Maneiro Rey, María
author
Perkins, Elizabeth
author
Howard, Julie A.
author
Deery, Michael J.
author
Chalker, Justin M.
author
Corzana, Francisco
author
Jiménez Osés, Gonzalo
author
Bernardes, Gonçalo J.L.
author
2018
Site-selective chemical conjugation of synthetic molecules to proteins expands their functional and therapeutic capacity. Current protein modification methods, based on synthetic and biochemical technologies, can achieve site selectivity, but these techniques often require extensive sequence engineering or are restricted to the N- or C-terminus. Here we show the computer-assisted design of sulfonyl acrylate reagents for the modification of a single lysine residue on native protein sequences. This feature of the designed sulfonyl acrylates, together with the innate and subtle reactivity differences conferred by the unique local microenvironment surrounding each lysine, contribute to the observed regioselectivity of the reaction. Moreover, this site selectivity was predicted computationally, where the lysine with the lowest pKa was the kinetically favored residue at slightly basic pH. Chemoselectivity was also observed as the reagent reacted preferentially at lysine, even in those cases when other nucleophilic residues such as cysteine were present. The reaction is fast and proceeds using a single molar equivalent of the sulfonyl acrylate reagent under biocompatible conditions (37 °C, pH 8.0). This technology was demonstrated by the quantitative and irreversible modification of five different proteins including the clinically used therapeutic antibody Trastuzumab without prior sequence engineering. Importantly, their native secondary structure and functionality is retained after the modification. This regioselective lysine modification method allows for further bioconjugation through aza-Michael addition to the acrylate electrophile that is generated by spontaneous elimination of methanesulfinic acid upon lysine labeling. We showed that a protein–antibody conjugate bearing a site-specifically installed fluorophore at lysine could be used for selective imaging of apoptotic cells and detection of Her2+ cells, respectively. This simple, robust method does not require genetic engineering and may be generally used for accessing diverse, well-defined protein conjugates for basic biology and therapeutic studies
J. Am. Chem. Soc. 2018, 140, 11, 4004–4017
0002-7863
http://hdl.handle.net/10347/24310
10.1021/jacs.7b12874
1520-5126
Reagents
Modification
Peptides and proteins
Monomers
Organic compounds
Chemo- and Regioselective Lysine Modification on Native Proteins
oai:minerva.usc.es:10347/312062024-02-22T08:15:15Zcom_10347_2988com_10347_2889com_10347_227col_10347_11762
00925njm 22002777a 4500
dc
Velasco Rubio, Álvaro
author
Martínez Balart, Pol
author
Álvarez-Constantino, Andrés M.
author
Fañanás-Mastral, Martín
author
2023-06-29
The direct functionalization of alkanes represents a very important challenge in the goal to develop more atom-efficient and clean C–C bond forming reactions. These processes, however, are hampered by the low reactivity of the aliphatic C–H bonds. Photocatalytic processes based on hydrogen atom transfer C–H bond activation strategies have become a useful tool to activate and functionalize these inert compounds. In this article, we summarize the main achievements in this field applied to the development of C–C bond forming reactions, and we discuss the key mechanistic features that enable these transformation
Chem. Commun., 2023,59, 9424-9444
0009-241X
10.1039/D3CC02790B
http://hdl.handle.net/10347/31206
2050-5620
C–C bond formation via photocatalytic direct functionalization of simple alkanes
oai:minerva.usc.es:10347/232022023-07-10T06:21:40Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Martínez Negro, María
author
Guerrero Martínez, Andrés
author
García Río, Luis
author
Domènech, Òscar
author
Aicart, Emilio
author
Tros de Ilarduya, Conchita
author
Junquera, Elena
author
2018
A multidisciplinary strategy, including bothbiochemical and biophysical studies, was proposed here toevaluate the potential of lipid nanoaggregates consisting of amixture of a gemini−bolaamphiphilic lipid (C6C22C6) and thewell-known helper lipid 1,2-dioleoyl-sn-glycero-3-phosphatidy-lethanolamine (DOPE) to transfect plasmid DNA into livingcells in an efficient and safe way. For that purpose, severalexperimental techniques were employed, such as zeta potential(phase analysis light scattering methodology), agarose gelelectrophoresis (pDNA compaction and pDNA protectionassays), small-angle X-ray scattering, cryo-transmission electronmicroscopy, atomic force microscopy,fluorescence-assisted cellsorting, luminometry, and cytotoxicity assays. The resultsrevealed that the cationic lipid and plasmid offer only 70 and30% of their nominal positive (=++q2.0nom,C C C6226) and negative charges (=−−q2/bpnom,pDNA), respectively. Upon mixing withDOPE, they form lipoplexes that self-aggregate in typical multilamellar Lαlyotropic liquid-crystal nanostructures with sizes in therange of 100−200 nm and low polydispersities, very suitablyfitted to remain in the bloodstream and cross the cell membrane.Interestingly, these nanoaggregates were able to compact, protect (from the degrading effect of DNase I), and transfect two DNAplasmids (pEGFP-C3, encoding the greenfluorescent protein, and pCMV-Luc, encoding luciferase) into COS-7 cells, with anefficiency equal or even superior to that of the universal control Lipo2000*, as long as the effective +/−charge ratio wasmaintained higher than 1 but reasonably close to electroneutrality. Moreover, this transfection process was not cytotoxic becausethe viability of COS-7 cells remained at high levels, greater than 80%. All of these features make the C6C22C6/DOPE nanosysteman optimal nonviral gene nanocarrier in vitro and a potentially interesting candidate for future in vivo experiments
ACS Omega 2018, 3, 1, 208–217
2470-1343
http://hdl.handle.net/10347/23202
10.1021/acsomega.7b01657
Vesicles
Lipids
Cytosine
Genetics
Chemical structure
Multidisciplinary approach to the transfection of plasmid DNA by a nonviral nanocarrier based on a Gemini-Bolaamphiphilic hybrid lipid
oai:minerva.usc.es:10347/123792023-07-10T06:12:57Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Bernal Albert, Paloma
author
Faustino, Hélio
author
Gimeno, Ana
author
Asensio, Gregorio
author
Mascareñas Cid, José Luis
author
López García, Fernando
author
2014-11-19
α,β-Unsaturated N,N-dialkyl hydrazones undergo a mild [2 + 2] cycloaddition to allenamides when treated with a suitable gold catalyst. The method, which represents the first application of N,N-dialkyl hydrazones in gold catalysis, is
compatible with a wide variety of substituents at the alkenyl moiety of the hydrazone component, proceeds with excellent levels of regio- and diastereoselectivity, and provides densely substituted cyclobutanes with good to excellent yields
Bernal-Albert, P., Faustino, H., Gimeno, A., Asensio, G., Mascareñas, J.L. and López, F. (2014). Gold(I)-Catalyzed Intermolecular Cycloaddition of Allenamides with α,β-Unsaturated Hydrazones: Efficient Access to Highly Substituted Cyclobutanes. Org. Lett., 2014,16 (23), pp. 6196–6199. doi: 10.1021/ol503121q
1523-7060
E-ISSN 1523-7052
http://hdl.handle.net/10347/12379
10.1021/ol503121q
Gold
Catalysis
Cycloaddition
Allenamides
Cyclobutanes
Hydrazones
Gold(I)-Catalyzed Intermolecular Cycloaddition of Allenamides with α,β-Unsaturated Hydrazones: Efficient Access to Highly Substituted Cyclobutanes
oai:minerva.usc.es:10347/184612023-07-10T06:16:48Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Cagiao Marcote, David
author
Varela Sandá, Iván
author
Fernández Casado, Jaime
author
Mascareñas Cid, José Luis
author
López García, Fernando
author
2018
Piperidine scaffolds are present in a wide range of bioactive natural products and are therefore considered as
highly valuable, privileged synthetic targets. In this manuscript, we describe a gold-catalyzed annulation strategy that allows a
straightforward assembly of piperidines and piperidine-containing aza-bridged products from readily available alkene-tethered
oxime ethers (or esters) and N-allenamides. Importantly, we demonstrate the advantages of using oxime derivatives over imines,
something pertinent to the whole area of gold catalysis, and provide relevant mechanistic experiments that shed light into the
factors affecting the annulation processes. Moreover, we also describe preliminary experiments demonstrating the viability of
enantioselective versions of the above reactions
Marcote, D., Varela, I., Fernández-Casado, J., Mascareñas, J., & López, F. (2018). Gold(I)-Catalyzed Enantioselective Annulations between Allenes and Alkene-Tethered Oxime Ethers: A Straight Entry to Highly Substituted Piperidines and aza-Bridged Medium-Sized Carbocycles. Journal Of The American Chemical Society, 140(48), 16821-16833. doi: 10.1021/jacs.8b10388
0002-7863
http://hdl.handle.net/10347/18461
10.1021/jacs.8b10388
1520-5126
Gold(I)–catalyzed enantioselective annulations between allenes and alkene-tethered oxime ethers: A straight entry to highly substituted piperidines and aza-bridged medium-sized carbocycles
oai:minerva.usc.es:10347/235192020-11-03T03:01:28Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Jespers, Willem
author
Oliveira, Ana
author
Prieto Díaz, Rubén
author
Majellaro, María
author
Åqvist, Johan
author
Sotelo Pérez, Eddy
author
Gutiérrez de Terán, Hugo
author
2017
The four receptors that signal for adenosine, A1, A2A, A2B and A3 ARs, belong to the superfamily of G protein-coupled receptors (GPCRs). They mediate a number of (patho)physiological functions and have attracted the interest of the biopharmaceutical sector for decades as potential drug targets. The many crystal structures of the A2A, and lately the A1 ARs, allow for the use of advanced computational, structure-based ligand design methodologies. Over the last decade, we have assessed the efficient synthesis of novel ligands specifically addressed to each of the four ARs. We herein review and update the results of this program with particular focus on molecular dynamics (MD) and free energy perturbation (FEP) protocols. The first in silico mutagenesis on the A1AR here reported allows understanding the specificity and high affinity of the xanthine-antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). On the A2AAR, we demonstrate how FEP simulations can distinguish the conformational selectivity of a recent series of partial agonists. These novel results are complemented with the revision of the first series of enantiospecific antagonists on the A2BAR, and the use of FEP as a tool for bioisosteric design on the A3AR
Jespers, W.; Oliveira, A.; Prieto-Díaz, R.; Majellaro, M.; Åqvist, J.; Sotelo, E.; Gutiérrez-de-Terán, H. Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors. Molecules 2017, 22, 1945
http://hdl.handle.net/10347/23519
10.3390/molecules22111945
1420-3049
Free energy perturbation (FEP)
G protein-coupled receptors (GPCRs)
Molecular dynamics (MD) simulations
Structure-based drug design (SBDD)
Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors
oai:minerva.usc.es:10347/211542023-07-10T06:12:40Zcom_10347_2988com_10347_2889com_10347_227com_10347_2937com_10347_2892com_10347_2888com_10347_2923com_10347_2891com_10347_2925col_10347_11762col_10347_11886col_10347_12110col_10347_9937
00925njm 22002777a 4500
dc
Cabrerizo Vílchez, Miguel Ángel
author
Fernández García, José Ramón
author
Fernández Rodríguez, Miguel Ángel
author
García Río, Luis
author
Muñiz Castiñeira, María del Carmen
author
Núñez García, Cristina
author
2019
This paper introduces a new mathematical model that is used to compute either the interfacial tension of quiescent axisymmetric pendant/sessile drops and pendant/captive bubbles. This model consists of the Young–Laplace equation, that describes interface shape, together with suitable boundary conditions that guarantee a prescribed volume of drops/bubbles and a fixed position in the capillary. In order to solve the problem numerically, the Young–Laplace equation is discretized by using numerical differentiation and the numerical solutions are obtained applying the well-know Newton method. The paper contains a validation of the new methodology presented for what theoretical bubble/drops are used. Finally, some numerical results are presented for both drops and bubbles of water as well as several surfactant solutions to demonstrate the applicability, versatility and reproducibility of the proposed methodology
Cabrerizo-Vilchez, M., Fernández, J., Fernández-Rodríguez, M., García-Río, L., Muñiz, M., & Núñez, C. (2019). Interfacial tension measurements using a new axisymmetric drop/bubble shape technique. RSC Advances, 9(28)
http://hdl.handle.net/10347/21154
10.1039/C9RA00940J
2046-2069
Axisymmetric bubble
Mathematical models
Axisymmetric drop
Young–Laplace equation
Interfacial tension measurements using a new axisymmetric drop/bubble shape technique
oai:minerva.usc.es:10347/235822023-07-10T06:12:33Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888com_10347_2927col_10347_11762col_10347_9937col_10347_12292
00925njm 22002777a 4500
dc
González Fernández, Daniel
author
Torneiro Abuín, Mercedes
author
Lazzari, Massimo
author
2020
We provide fundamental guidelines in the form of a tutorial to be taken into account for the preparation and characterization of a specific class of poly(ethylene glycol) (PEG) derivatives, namely azide-terminated PEGs. Special attention is given to the effect of these chain end groups and their precursors on properties affecting the PEGylation of proteins, nanoparticles and nanostructured surfaces. Notwithstanding the presence of 13C satellite peaks, we show that 1H NMR enables not only the routine quantitative determination of chain-end substitution, but is also a unique method to calculate the absolute number average molecular weight of PEG derivatives. In the use of size exclusion chromatography to get molecular weight distributions, we highlight the importance of distinguishing between eventual secondary reactions involving molecular weight changes and the formation of PEG complexes due to residual amounts of metal cations from reactants. Finally, we show that azide end groups affect PEG melting behavior. In contrast to oxygen-containing end groups, azides do not interact with PEG segments, thus inducing defect formation in the crystal lattice and the reduction of crystal sizes. Melting temperature and degree of crystallinity decrease become especially relevant for PEGs with very low molecular weight, and its comprehension is particularly important for solid-state applications
González-Fernández, D.; Torneiro, M.; Lazzari, M. Some Guidelines for the Synthesis and Melting Characterization of Azide Poly(ethylene glycol) Derivatives. Polymers 2020, 12, 1269
http://hdl.handle.net/10347/23582
10.3390/polym12061269
2073-4360
Poly(ethylene glycol)
PEGylation
Nanoparticles
Functionalization
Azide-terminated
Melting behavior
Some Guidelines for the Synthesis and Melting Characterization of Azide Poly(ethylene glycol) Derivatives
oai:minerva.usc.es:10347/169512020-01-31T08:48:36Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Pinto, Luiz F.
author
Riguera Vega, Ricardo
author
Fernández Megía, Eduardo
author
2013
The characteristic distribution of transverse relaxation times (T2) within dendrimers (shorter values at the core than the periphery) can be exploited in T2-edited 1D and 2D NMR experiments for the stepwise filtering of internal nuclei according to their topology within the dendritic structure. The resulting filtered spectra, which can be conceived as corresponding to virtual hollow dendrimers, benefit from reduced signal overlap, thus facilitating signal assignment and characterization. The generality of the method as a powerful tool in structural and end-group analysis has been confirmed with various dendritic families and nuclei (1H, 13C, 31P)
Pinto, L., Riguera, R., & Fernandez-Megia, E. (2013). Stepwise Filtering of the Internal Layers of Dendrimers by Transverse-Relaxation-Edited NMR. Journal Of The American Chemical Society, 135(31), 11513-11516. doi: 10.1021/ja4059348
0002-7863
http://hdl.handle.net/10347/16951
10.1021/ja4059348
1520-5126
Stepwise Filtering of the Internal Layers of Dendrimers by Transverse-Relaxation-Edited NMR
oai:minerva.usc.es:10347/169852023-07-10T06:12:11Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Lobato, Rubén
author
Veiga, Alberte X.
author
Pérez-Vázquez, Jaime
author
Fernández-Nieto, Fernando
author
Paleo, M. Rita
author
Sardina, F. Javier
author
2013
A series of dibenzo [n.2.2] bicyclic compounds (n = 2–20) were prepared in one step and good yields starting from dimethyl anthracene-9,10-dicarboxylate. Reduction of the aromatic diester using lithium/naphthalene led to a bis-enolate that was cyclized with a variety of bis-electrophiles. The ease of the cyclization is probably due to the puckered conformation of the intermediate formed after the first alkylation step, in which the newly introduced chain that will become the bridge portion occupies a pseudoaxial position, positioning the leaving group close to the enolate nucleophile in the macrocyclization step
Lobato, R., Veiga, A., Pérez-Vázquez, J., Fernández-Nieto, F., Paleo, M., & Sardina, F. (2013). A One-Step, Versatile Synthesis of Dibenzo [n.2.2] Macrobicyclic Compounds via a Conformation-Directed Macrocyclization Reaction. Organic Letters, 15(16), 4090-4093. doi: 10.1021/ol4016767
1523-7060
http://hdl.handle.net/10347/16985
10.1021/ol4016767
1523-7052
A One-Step, Versatile Synthesis of Dibenzo [n.2.2] Macrobicyclic Compounds via a Conformation-Directed Macrocyclization Reaction
oai:minerva.usc.es:10347/169822020-01-31T09:07:47Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Navarro-Vázquez, Armando
author
Santamaría Fernández, Raquel
author
Sardina, F. Javier
author
2018-05-17
MSpin‐JCoupling is a modular program for the prediction of scalar couplings using a large variety of Karplus relationships. The program was specially designed for small molecule analysis and can be run in graphical or command‐line mode. The architecture of the program is highly modular, and new equations can be rapidly implemented, through a complete C++ programming interface, and deployed as run‐time loadable plugins
Navarro-Vázquez, A., Santamaría-Fernández, R., & Sardina, F. (2018). MSpin-JCoupling. A modular program for prediction of scalar couplings and fast implementation of Karplus relationships. Magnetic Resonance In Chemistry, 56(6), 505-512. doi: 10.1002/mrc.4667
http://hdl.handle.net/10347/16982
10.1002/mrc.4667
1097-458X
Karplus equation
Open source
Scalar couplings
Software
MSpin‐JCoupling. A modular program for prediction of scalar couplings and fast implementation of Karplus relationships
oai:minerva.usc.es:10347/165682023-07-10T06:16:07Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Martínez Calvo, Miguel
author
Mascareñas Cid, José Luis
author
2018-01-29
Organometallic catalysis has allowed the development of an impressive number of chemical transformations that could not be achieved using classical methodologies. Most of these reactions have been accomplished in organic solvents, and in many cases in the absence of water, and under air-free conditions. The increasing pressure to develop more sustainable transformations has stimulated the discovery of metal-catalyzed reactions that can take place in water. A particularly attractive extension of this chemistry consists of the use of biological relevant aqueous solvents, as this might set the basis to translate catalytic metal complexes to biological settings. While this research field is in its infancy, along the last ten years there have been an increasing number of reports demonstrating the viability of achieving metal-promoted transformations in biologically relevant contexts. In this review, that does not intend to be comprehensive, we summarize the most significant advances in the area, and highlight some of the more important difficulties that must be faced when trying to design biocompatible organometallic catalysts, such us stability, cell uptake, bioorthogonality and toxicity. We will manly focus on transition metal systems which have been shown to keep their activity in complex aqueous buffers and inside living cells
Martínez-Calvo, M., & Mascareñas, J. (2018). Organometallic catalysis in biological media and living settings. Coordination Chemistry Reviews, 359, 57-79. http://dx.doi.org/10.1016/j.ccr.2018.01.011
0010-8545
http://hdl.handle.net/10347/16568
10.1016/j.ccr.2018.01.011
Organometallic
Bioorthogonal
Transition metal catalysis
Living cells
Artificial metalloenzymes
Organometallic catalysis in biological media and living settings
oai:minerva.usc.es:10347/169212020-01-31T07:39:02Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Costas, Celina
author
López Puente, Vanesa
author
Bodelón, Gustavo
author
González Bello, Concepción
author
Pérez Juste, Jorge
author
Pastoriza Santos, Isabel
author
Liz-Marzán, Luis M.
author
2015-04-30
Many members of the LuxR family of quorum sensing (QS) transcriptional activators, including LasR of Pseudomonas aeruginosa, are believed to require appropriate acyl-homoserine lactone (acyl-HSL) ligands to fold into an active conformation. The failure to purify ligand-free LuxR homologues in nonaggregated form at the high concentrations required for their structural characterization has limited the understanding of the mechanisms by which QS receptors are activated. Surface-enhanced Raman scattering (SERS) is a vibrational spectroscopy technique that can be applied to study proteins at extremely low concentrations in their active state. The high sensitivity of SERS has allowed us to detect molecular interactions between the ligand-binding domain of LasR (LasRLBD) as a soluble apoprotein and modulators of P. aeruginosa QS. We found that QS activators and inhibitors produce differential SERS fingerprints in LasRLBD, and in combination with molecular docking analysis provide insight into the relevant interaction mechanism. This study reveals signal-specific structural changes in LasR upon ligand binding, thereby confirming the applicability of SERS to analyze ligand-induced conformational changes in proteins
Costas, C., López-Puente, V., Bodelón, G., González-Bello, C., Pérez-Juste, J., Pastoriza-Santos, I., & Liz-Marzán, L. (2015). Using Surface Enhanced Raman Scattering to Analyze the Interactions of Protein Receptors with Bacterial Quorum Sensing Modulators. ACS Nano, 9(5), 5567-5576. doi: 10.1021/acsnano.5b01800
1936-0851
http://hdl.handle.net/10347/16921
10.1021/acsnano.5b01800
1936-086X
Nanoplasmonics
SERS
Quorum sensing
Protein receptors
Pseudomonas aeruginosa
Using Surface Enhanced Raman Scattering to Analyze the Interactions of Protein Receptors with Bacterial Quorum Sensing Modulators
oai:minerva.usc.es:10347/188812021-02-01T12:38:30Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Hirose, Daisuke
author
Isobe, Asahi
author
Quiñoá Cabana, Emilio
author
Freire Iribarne, Félix Manuel
author
Maeda, Katsuhiro
author
2019-05-07
An unprecedented three-state switchable chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) was developed using a helical poly(phenylacetylene) bearing a chiral (R)-α-methoxyphenylacetic acid residue as the pendant (poly-1). The left- and right-handed helical conformations were induced in poly-1-based CSP upon coordination with a catalytic amount of soluble sodium and cesium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate salts (MBArF), respectively, which are soluble in the HPLC conditions [hexane–2-propanol (95:5, v/v)]. The switch between the two different helical states of poly-1 can be easily achieved by rinsing the poly-1-based CSP with MeOH and the subsequent addition of the proper MBArF salt. Using this dynamic helical CSP, we demonstrate how changes on the orientation of the secondary structure of a chiral polymer (right-handed, left-handed, and racemic helices) can alter and even invert the elution order of the enantiomers. This study was done without adding chiral additives or changing the mobile phase, which could produce changes on the retention times and make it more difficult to determine the role of the secondary structure during the chiral recognition process
Hirose, D., Isobe, A., Quiñoá, E., Freire, F., & Maeda, K. (2019). Three-State Switchable Chiral Stationary Phase Based on Helicity Control of an Optically Active Poly(phenylacetylene) Derivative by Using Metal Cations in the Solid State. Journal Of The American Chemical Society, 141(21), 8592-8598. doi: 10.1021/jacs.9b03177
0002-7863
http://hdl.handle.net/10347/18881
10.1021/jacs.9b03177
1520-5126
Three-State Switchable Chiral Stationary Phase Based on Helicity Control of an Optically Active Poly(phenylacetylene) Derivative by Using Metal Cations in the Solid State
oai:minerva.usc.es:10347/288272022-06-22T02:02:49Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Gutiérrez Hernández, Sara
author
Tomás Gamasa, María
author
2022
Translating the power of transition metal catalysis to the native habitats of enzymes can significantly expand the possibilities of interrogating or manipulating natural biological systems, including living cells and organisms. This is especially relevant for organometallic reactions that have shown great potential in the field of organic synthesis, like the metal-catalyzed transfer of carbenes. While, at first sight, performing metal carbene chemistry in aqueous solvents, and especially in biologically relevant mixtures, does not seem obvious, in recent years there has been a growing number of reports demonstrating the feasibility
of the task. Either using small molecule metal catalysts or artificial metalloenzymes, a number of carbene transfer reactions that tolerate aqueous and biorelevant media are being developed. This review intends to summarize the most relevant contributions, and establish the state of the art in this emerging research field
Chem. Sci., 2022, 13, 6478-6495
http://hdl.handle.net/10347/28827
10.1039/d2sc00721e
1742-2183
Organometallic catalysis in aqueous and biological environments: harnessing the power of metal carbenes
oai:minerva.usc.es:10347/169472023-07-10T06:12:42Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
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dc
Pinto, Luiz F.
author
Correa, Juan
author
Zhao, Libo
author
Riguera Vega, Ricardo
author
Fernández Megía, Eduardo
author
2018-03-12
The paramagnetic spin relaxation filter is described for the rapid NMR screening of intermolecular interactions between ligands and macromolecular anionic receptors with large transverse relaxation enhancements (R2p). The addition of micromolar concentrations of Gd3+ to the mixture produces the immediate broadening/suppression of the NMR signals of interacting species while leaving unaffected those of noncompetitive binders (one-dimensional and two-dimensional experiments). The method is highly sensitive, unveiling interactions that are too weak to generate changes in chemical shifts or relaxation times. It is operationally very simple and hence, it is amenable to ready implementation by nonspecialists. Examples of application such as detecting the formation of interpolymer complexes, cyclodextrin host–guest interactions, and the screening of DNA ligands are included that demonstrate the reliability and broad applicability of the method
Pinto, L., Correa, J., Zhao, L., Riguera, R., & Fernandez-Megia, E. (2018). Fast NMR Screening of Macromolecular Complexes by a Paramagnetic Spin Relaxation Filter. ACS Omega, 3, 3, 2974-2983. doi: 10.1021/acsomega.7b02074
http://hdl.handle.net/10347/16947
10.1021/acsomega.7b02074
2470-1343
Fast NMR Screening of Macromolecular Complexes by a Paramagnetic Spin Relaxation Filter
oai:minerva.usc.es:10347/184732023-07-10T06:16:17Zcom_10347_2897com_10347_2890com_10347_2888com_10347_227com_10347_2988com_10347_2889com_10347_2927com_10347_2891col_10347_12277col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Sánchez López, Mateo Isidro
author
Martínez Costas, José Manuel
author
Mascareñas Cid, José Luis
author
Vázquez Sentís, Marco Eugenio
author
2014
We report the discovery of a fluorogenic dye, N1,N3-di(2-aminidonaphthalen-6-yl) propane-1,3-diamine, MitoBlue, which selectively stains functional mitochondria while displaying low toxicity, bright blue emission, and high resistance to photobleaching. Additionally, we show that a biotin-labeled MitoBlue derivative can be used as a handle for the delivery of streptavidin-tagged species to the mitochondria
Sánchez, M., Martínez-Costas, J., Mascareñas, J., & Vázquez, M. (2014). MitoBlue: A Nontoxic and Photostable Blue-Emitting Dye That Selectively Labels Functional Mitochondria. ACS Chemical Biology, 9(12), 2742-2747. doi: 10.1021/cb500552f
1554-8929
http://hdl.handle.net/10347/18473
10.1021/cb500552f
1554-8937
MitoBlue: A Nontoxic and Photostable Blue-Emitting Dye That Selectively Labels Functional Mitochondria
oai:minerva.usc.es:10347/225162020-05-25T02:01:39Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Fernández Dueñas, Víctor
author
Azuaje Guerrero, Jhonny Alberto
author
Morató, Xavier
author
Cordobilla, Begoña
author
Domingo, Joan Carles
author
Sotelo Pérez, Eddy
author
Ciruela, Francisco
author
2017
Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson’s disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine. Furthermore, DHA displays properties that may lead to its use as a neuroprotective agent. In the present study, we constructed a novel bivalent ligand covalently linking caffeine and DHA and assessed its pharmacological activity and safety profile in a simple cellular model. Interestingly, the new bivalent ligand presented higher potency as an A2AR inverse agonist than caffeine alone. We also determined the range of concentrations inducing toxicity both in a heterologous system and in primary striatal cultures. The novel strategy presented here of attaching DHA to caffeine may enable increased effects of the drug at desired sites, which could be of interest for the treatment of PD
Fernández-Dueñas, V.; Azuaje, J.; Morató, X.; Cordobilla, B.; Domingo, J.C.; Sotelo, E.; Ciruela, F. Synthesis and Characterization of a New Bivalent Ligand Combining Caffeine and Docosahexaenoic Acid. Molecules 2017, 22, 366.
http://hdl.handle.net/10347/22516
10.3390/molecules22030366
1420-3049
Adenosine A2A receptor
Caffeine
Docosahexaenoic acid (DHA)
Inverse agonism
Synthesis and characterization of a new bivalent ligand combining caffeine and docosahexaenoic acid
oai:minerva.usc.es:10347/310132024-02-23T07:24:54Zcom_10347_2989com_10347_2889com_10347_227com_10347_2988com_10347_2927com_10347_2891com_10347_2888col_10347_9764col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Gioé-Gallo, Claudia
author
Ortigueira Noya, Sandra
author
Brea Floriani, José Manuel
author
Raïch, Iu
author
Azuaje, Jhonny
author
Paleo Pillado, María Rita
author
Majellaro, Maria
author
Loza García, María Isabel
author
Salas, Cristian O.
author
García Mera, Xerardo
author
Navarro, Gemma
author
Sotelo Pérez, Eddy
author
2023-05-22
Synthetic cannabinoid receptor agonists (SCRAs) constitute the largest and most defiant group of abuse designer drugs. These new psychoactive substances (NPS), developed as unregulated alternatives to cannabis, have potent cannabimimetic effects and their use is usually associated with episodes of psychosis, seizures, dependence, organ toxicity and death. Due to their ever-changing structure, very limited or nil structural, pharmacological, and toxicological information is available to the scientific community and the law enforcement offices. Here we report the synthesis and pharmacological evaluation (binding and functional) of the largest and most diverse collection of enantiopure SCRAs published to date. Our results revealed novel SCRAs that could be (or may currently be) used as illegal psychoactive substances. We also report, for the first time, the cannabimimetic data of 32 novel SCRAs containing an (R) configuration at the stereogenic center. The systematic pharmacological profiling of the library enabled the identification of emerging Structure-Activity Relationship (SAR) and Structure-Selectivity Relationship (SSR) trends, the detection of ligands exhibiting incipient cannabinoid receptor type 2 (CB2R) subtype selectivity and highlights the significant neurotoxicity of representative SCRAs on mouse primary neuronal cells. Several of the new emerging SCRAs are currently expected to have a rather limited potential for harm, as the evaluation of their pharmacological profiles revealed lower potencies and/or efficacies. Conceived as a resource to foster collaborative investigation of the physiological effects of SCRAs, the library obtained can contribute to addressing the challenge posed by recreational designer drugs
Biomedicine & Pharmacotherapy 164 (2023) 114934
0753-3322
http://hdl.handle.net/10347/31013
10.1016/j.biopha.2023.114934
Synthetic cannabinoid receptor agonists
SCRAs
Synthetic cannabinoids
NPS
Abuse drugs
Designer drugs
CB1
CB2
Cannabinoids
Indole
Indazole
Pharmacological insights emerging from the characterization of a large collection of synthetic cannabinoid receptor agonists designer drugs
oai:minerva.usc.es:10347/197602023-07-10T06:11:29Zcom_10347_2989com_10347_2889com_10347_227com_10347_2988col_10347_9764col_10347_11762
00925njm 22002777a 4500
dc
Kalash, Leen
author
Val García, Cristina
author
Azuaje Guerrero, Jhonny Alberto
author
Loza García, María Isabel
author
Svensson, Fredrik
author
Zoufir, Azedine
author
Mervin, Lewis
author
Ladds, Graham
author
Brea Floriani, José Manuel
author
Glen, Robert
author
Sotelo Pérez, Eddy
author
Bender, Andreas
author
2017
Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at
multiple targets is required to produce a clinical efect. In particular, suitable compounds may be useful in treating
neurodegenerative diseases by promoting neuronal survival in a synergistic manner via their multi-target activity at
the adenosine A1 and A2A receptors (A1R and A2AR) and phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, in this work we describe a computational method for the design of synthetically feasible
ligands that bind to A1 and A2A receptors and inhibit phosphodiesterase 10A (PDE10A), involving a retrosynthetic
approach employing in silico target prediction and docking, which may be generally applicable to multi-target
compound design at several target classes. This approach has identifed 2-aminopyridine-3-carbonitriles as the frst
multi-target ligands at A1R, A2AR and PDE10A, by showing agreement between the ligand and structure based predictions at these targets. The series were synthesized via an efcient one-pot scheme and validated pharmacologically as
A1R/A2AR–PDE10A ligands, with IC50 values of 2.4–10.0 μM at PDE10A and Ki
values of 34–294 nM at A1R and/or A2AR.
Furthermore, selectivity profling of the synthesized 2-amino-pyridin-3-carbonitriles against other subtypes of both
protein families showed that the multi-target ligand 8 exhibited a minimum of twofold selectivity over all tested oftargets. In addition, both compounds 8 and 16 exhibited the desired multi-target profle, which could be considered
for further functional efcacy assessment, analog modifcation for the improvement of selectivity towards A1R, A2AR
and PDE10A collectively, and evaluation of their potential synergy in modulating cAMP levels
Kalash, L., Val, C., Azuaje, J., Loza, M., Svensson, F., & Zoufir, A. et al. (2017). Computer-aided design of multi-target ligands at A1R, A2AR and PDE10A, key proteins in neurodegenerative diseases. Journal Of Cheminformatics, 9(1). doi: 10.1186/s13321-017-0249-4
1758-2946
http://hdl.handle.net/10347/19760
10.1186/s13321-017-0249-4
Multi-target ligands
Adenosine receptor ligands
PDE10A inhibitors
Target prediction
Drug design
Docking
QSAR
Computer-aided design of multi-target ligands at A1R, A2AR and PDE10A, key proteins in neurodegenerative diseases
oai:minerva.usc.es:10347/183362023-07-10T06:16:44Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Sánchez López, Mateo Isidro
author
Penas Tallón, Cristina
author
Vázquez Sentís, Marco Eugenio
author
Mascareñas Cid, José Luis
author
2014
Attachment of alloc protecting groups to the amidine units of fluorogenic DNA-binding bisbenzamidines or to the amino groups of ethidium bromide leads to a significant reduction of their DNA affinity. More importantly, the active DNA-binding species can be readily regenerated by treatment with ruthenium catalysts in aqueous conditions, even in cell cultures. The catalytic chemical uncaging can be easily monitored by fluorescence microscopy, because the protected products display both different emission properties and cell distribution to the parent compounds
Sánchez, M., Penas, C., Vázquez, M., & Mascareñas, J. (2014). Metal-catalyzed uncaging of DNA-binding agents in living cells. Chem. Sci., 5(5), 1901-1907. doi: 10.1039/c3sc53317d
http://hdl.handle.net/10347/18336
10.1039/C3SC53317D
2041-6539
Metal-catalyzed uncaging of DNA-binding agents in living cells
oai:minerva.usc.es:10347/167362023-07-10T06:13:00Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Rodríguez-Vázquez, Nuria
author
Amorín López, Manuel
author
Granja Guillán, Juan Ramón
author
Alfonso, Ignacio
author
2016-03-21
A cyclic octapeptide composed of hydroxy-functionalized γ-amino acids folds in a "V-shaped" conformation that allows the selective recognition of anions such as chloride, nitrate, and carbonate. The process involves the simultaneous self-assembly of six peptide subunits and the recognition of four anions to form a tetrahedral structure, in which the anions are located at the corners of the resulting structure. Each anion is coordinated to three different peptides. The structure was fully characterized by several techniques, including NMR spectroscopy and X-ray diffraction, and the material was able to facilitate the transmembrane transport of chloride ions
Rodríguez-Vázquez, N., García-Fandiño, R., Amorín, M., & Granja, J. (2016). Anion recognition self-assembly α,γ-cyclic peptide to form spherical clusters. Angewandte Chemie internationa edition,55(14):4504-8. Doi: 10.1002/anie.201511857
1433-7851
http://hdl.handle.net/10347/16736
10.1002/anie.201511857
1521-3773
Anionrecognition
Cyclic peptide
Self-assembling
Supramolecular chemistry
Transport
Anion recognition and induced self-assembly of an alpha,gamma-cyclic peptide to form spherical clusters
oai:minerva.usc.es:10347/248502023-07-10T06:16:19Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
González González, José Manuel
author
Cendón Mariño, Borja
author
Mascareñas Cid, José Luis
author
Gulías Costa, Moisés
author
2021
Enantioenriched, six-membered azacycles are essential structural motifs in many products of pharmaceutical or agrochemical interest. Here we report a simple and practical method for enantioselective assembly of tetrahydropyridines, which is paired to a kinetic resolution of α-branched allyltriflamides. The reaction consists of a formal (4+2) cycloaddition between the allylamine derivatives and allenes and is initiated by a palladium(II)-catalyzed C–H activation process. Both the chiral allylamide precursors and the tetrahydropyridine adducts were successfully obtained in high yields, with excellent enantioselectivity (up to 99% ee) and selectivity values of up to 127
J. Am. Chem. Soc. 2021, 143, 10, 3747–3752
0002-7863
http://hdl.handle.net/10347/24850
10.1021/jacs.1c01929
1520-5126
Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C–H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines
oai:minerva.usc.es:10347/183352023-07-10T06:16:44Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Learte Aymamí, Soraya
author
Curado, Natalia
author
Rodríguez Villar, Jéssica
author
Vázquez Sentís, Marco Eugenio
author
Mascareñas Cid, José Luis
author
2017
A fragment of the DNA basic region (br) of the GCN4 bZIP transcription factor has been modified to include two His residues at designed i and i+4 positions of its N-terminus. The resulting monomeric peptide (brHis2) does not bind to its consensus target DNA site (5′-GTCAT-3′). However, addition of Pd(en)Cl2 (en, ethylenediamine) promotes a high-affinity interaction with exquisite selectivity for this sequence. The peptide–DNA complex is disassembled by addition of a slight excess of a palladium chelator, and the interaction can be reversibly switched multiple times by playing with controlled amounts of either the metal complex or the chelator. Importantly, while the peptide brHis2 fails to translocate across cell membranes on its own, addition of the palladium reagent induces an efficient cell internalization of this peptide. In short, we report (1) a designed, short peptide that displays highly selective, major groove DNA binding, (2) a reversible, metal-dependent DNA interaction, and (3) a metal-promoted cell internalization of this basic peptide
Learte-Aymamí, S., Curado, N., Rodríguez, J., Vázquez, M., & Mascareñas, J. (2017). Metal-Dependent DNA Recognition and Cell Internalization of Designed, Basic Peptides. Journal Of The American Chemical Society, 139(45), 16188-16193. doi: 10.1021/jacs.7b07422
0002-7863
http://hdl.handle.net/10347/18335
10.1021/jacs.7b07422
1520-5126
Metal-Dependent DNA Recognition and Cell Internalization of Designed, Basic Peptides
oai:minerva.usc.es:10347/170082020-04-24T15:12:45Zcom_10347_2988com_10347_2889com_10347_227com_10347_2926com_10347_2891com_10347_2888com_10347_2927col_10347_11762col_10347_15773col_10347_12292
00925njm 22002777a 4500
dc
Rama, Gustavo
author
Ardá, Ana
author
Maréchal, Jean-Didier
author
Gamba, Ilaria
author
Ishida, Hitoshi
author
Jiménez Barbero, Jesús
author
Vázquez Sentís, Marco Eugenio
author
Vázquez López, Miguel
author
2012-05-03
Playing into our hands: The achiral bipyridine amino acid fluorenylmethyloxycarbonyl 5‐amino‐3‐oxapentanoic acid (Fmoc‐O1PenBpy‐OH) has been used for the solid‐phase synthesis of metallopeptides. Circular dichroism, molecular modeling, and NMR spectroscopic studies show that the chirality of the resulting metal complexes in aqueous solution is determined, and can thus be controlled, by the stereochemistry of one proline residue in the loop between the two coordinating O1PenBpy residues
Rama, G., Ardá, A. , Maréchal, J., Gamba, I., Ishida, H., Jiménez‐Barbero, J., Vázquez, M. E. and Vázquez López, M. (2012), Stereoselective Formation of Chiral Metallopeptides. Chem. Eur. J., 18: 7030-7035. doi:10.1002/chem.201201036
http://hdl.handle.net/10347/17008
10.1002/chem.201201036
1521-3765
Chirality
Ligand effects
Metallopeptides
Molecular modeling
NMR spectroscopy
Peptides
Stereoselective Formation of Chiral Metallopeptides
oai:minerva.usc.es:10347/206782023-07-10T06:13:11Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Méndez Ardoy, Alejandro
author
Reina Martín, Jose Juan
author
Montenegro García, Javier
author
2020
Tracking the pH with spatiotemporal resolution is a critical challenge for synthetic chemistry, chemical biology and beyond. Over the last decade different small probes and supramolecular systems have emerged for in celluloor in vivo pH tracking. However, pH reporting still presents critical limitations such as background reduction, sensor improved stability, cell targeting, endosomal escape, near and far infrared ratiometric pH tracking, adaptation to the new imaging techniques (i.e. super‐resolution), etc. These challenges will demand the combined efforts of synthetic and supramolecular chemistry working together to develop a next generation of smart materials that will resolve the current limitations. In this review we describe the recent advances in the synthesis of small fluorescent probes together with new supramolecular functional systems employed for pH tracking with emphasis in ratiometric probes. The combination of organic synthesis and stimuli‐responsive supramolecular functional materials will be essential to solve future challenges of pH tracking such as the improved signal to noise ratio, on target activation and microenvironment reporting
Méndez-Ardoy, A., Reina, J..J. and Montenegro, J. (2020), Synthesis and Supramolecular Functional Assemblies of Ratiometric pH Probes. Chem. Eur. J.. doi:10.1002/chem.201904834
0947-6539
http://hdl.handle.net/10347/20678
10.1002/chem.201904834
1521-3765
Fluorescent probes
Supramolecular Chemistry
Organic synthesis
Ratiometric probes
Synthesis and Supramolecular Functional Assemblies of Ratiometric pH Probes
oai:minerva.usc.es:10347/211022023-07-10T06:18:10Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Pi-Boleda, Bernat
author
Campos Torrado, María
author
Sans, Marta
author
Basavilbaso González, Antonio
author
Illa, Ona
author
Branchadell, Vicenç
author
Estévez Cabanas, Juan Carlos
author
Ortuño, Rosa M.
author
2019
New enantiomerically pure C16-alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (−)-shikimic acid. The hydroxyl groups in these compounds are free or, alternatively, they present full or partial protection. Their gelling abilities towards several solvents have been tested and rationalized by means of the combined use of Hansen solubility parameters, scanning electron microscopy (SEM), and circular dichroism (CD), as well as computational calculations. All the results allowed us to account for the capability of each type of organogelator to interact with different solvents and for the main mode of aggregation. Thus, compounds with fully protected hydroxyl groups are good organogelators for methanol and ethanol. In contrast, a related compound bearing three free hydroxyl groups is insoluble in water and polar solvents including alcohols but it is able to gelate some low-polarity solvents. This last behavior can be justified by strong hydrogen bonding between molecules of organogelator, which competes advantageously with polar solvent interactions. As an intermediate case, an organogelator with two free hydroxyl groups presents an ambivalent ability to gelate both apolar and polar solvents by means of two aggregation patterns. These involve hydrogen bonding interactions of the unprotected hydroxyl groups in apolar solvents and intermolecular interactions between amide groups in polar ones
Pi-Boleda, B.; Campos, M.; Sans, M.; Basavilbaso, A.; Illa, O.; Branchadell, V.; Estévez, J.C.; Ortuño, R.M. Synthesis and Gelling Abilities of Polyfunctional Cyclohexane-1,2-dicarboxylic Acid Bisamides: Influence of the Hydroxyl Groups. Molecules 2019, 24, 352
1420-3049
http://hdl.handle.net/10347/21102
10.3390/molecules24020352
Polyfunctional cycloalkane bisamides
Organogelator
Self-assembly
Chirality
Hydrogen bonds
Synthesis and Gelling Abilities of Polyfunctional Cyclohexane-1,2-dicarboxylic Acid Bisamides: Influence of the Hydroxyl Groups
oai:minerva.usc.es:10347/170222023-07-10T06:12:00Zcom_10347_2988com_10347_2889com_10347_227com_10347_2926com_10347_2891com_10347_2888com_10347_2927col_10347_11762col_10347_15773col_10347_12292
00925njm 22002777a 4500
dc
Gamba, Ilaria
author
Rama, Gustavo
author
Ortega-Carrasco, Elisabeth
author
Berardozzi, Roberto
author
Sánchez-Pedregal, Víctor M.
author
Di Bari, Lorenzo
author
Maréchal, Jean-Didier
author
Vázquez Sentís, Marco Eugenio
author
Vázquez López, Miguel
author
2016
We have applied solid-phase synthesis methods for the construction of tris(bipyridyl) peptidic ligands that coordinate Fe(II) ions with high affinity and fold into stable mononuclear metallopeptides. The main factors influencing the folding pathway and chiral control of the peptidic ligands around the metal ions have been studied both by experimental techniques (CD, UV-vis and NMR) and molecular modeling tools. Amongst the numerous molecular variables that have been studied, this study clearly illustrates how the chirality of a given set of aminoacids (proline in this case) of the peptide dictates the chirality of the metal center of the resulting metallopeptide. Moreover, the relatively hydrophobic peptidic models used in this work show that the most stable structures present reduced solvent contacts and, in counterpart, stabilize the cis configuration of the proline residues
Gamba, I., Rama, G., Ortega-Carrasco, E., Berardozzi, R., Sánchez-Pedregal, V., & Di Bari, L. et al. (2016). The folding of a metallopeptide. Dalton Transactions, 45(3), 881-885. doi: 10.1039/c5dt02797g
1477-9226
http://hdl.handle.net/10347/17022
10.1039/C5DT02797G
1477-9234
The folding of a metallopeptide
oai:minerva.usc.es:10347/169802023-07-10T06:12:11Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Pérez Saavedra, Borja
author
Vázquez Galiñanes, Nuria
author
Saá, Carlos
author
Fañanás Mastral, Martín
author
2017-08-02
A copper-catalyzed tandem carboarylation/cyclization of alkynyl phosphonates with diaryliodonium salts is reported. The reaction gives straightforward access to valuable cyclic enol phosphonates in good yields under mild conditions. This transformation entails an initial chemoselective arylation of the alkyne followed by an intramolecular trapping of an intermediate vinyl cation by the phosphoryl group. Observation of β-aryl rearrangements across the double bond in intermediates generated from 1,2-diaryl alkynes support the intermediacy of a vinyl cation
Borja Pérez-Saavedra, Nuria Vázquez-Galiñanes, Carlos Saá, and Martín Fañanás-Mastral ACS Catalysis 2017 7 (9), 6104-6109 DOI: 10.1021/acscatal.7b02434
http://hdl.handle.net/10347/16980
10.1021/acscatal.7b02434
2155-5435
Alkynes
Carbocations
Copper
Diaryliodonium salts
Phosphonates
Copper(I)-Catalyzed Tandem Carboarylation/Cyclization of Alkynyl Phosphonates with Diaryliodonium Salts
oai:minerva.usc.es:10347/262452021-05-22T02:05:05Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Dib, Nahir
author
Lépori, Cristian M.O.
author
Correa, N. Mariano
author
Silber, Juana
author
Falcone, R. Dario
author
García Río, Luis
author
2021
In this review, we deal with the formation and application of biocompatible water-in-oil microemulsions commonly known as reverse micelles (RMs). These RMs are extremely important to facilitate the dissolution of hydrophilic and hydrophobic compounds for biocompatibility in applications in drug delivery, food science, and nanomedicine. The combination of two wisely chosen types of compounds such as biocompatible non-polar solvents and ionic liquids (ILs) with amphiphilic character (surface-active ionic liquids, SAILs) can be used to generate organized systems that perfectly align with the Green Chemistry concepts. Thus, we describe the current state of SAILs (protic and aprotic) to prepare RMs using non-polar but safe solvents such as esters derived from fatty acids, among others. Moreover, the use of the biocompatible solvents as the external phase in RMs and microemulsions/nanoemulsions with the other commonly used biocompatible surfactants is detailed showing the diversity of preparations and important applications. As shown by multiple examples, the properties of the RMs can be modified by changes in the type of surfactant and/or external solvents but a key fact to note is that all these modifications generate novel systems with dissimilar properties. These interesting properties cannot be anticipated or extrapolated, and deep analysis is always required. Finally, the works presented provide valuable information about the use of biocompatible RMs, making them a green and promising alternative toward efficient and sustainable chemistry
Polymers 2021, 13(9), 1378; https://doi.org/10.3390/polym13091378
http://hdl.handle.net/10347/26245
10.3390/polym13091378
2073-4360
Reverse micelles
Ionic liquids
Surfactant
Biocompatible
IPM
Biocompatible Solvents and Ionic Liquid-Based Surfactants as Sustainable Components to Formulate Environmentally Friendly Organized Systems
oai:minerva.usc.es:10347/184862023-07-10T06:16:48Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Pazos Chantrero, Elena
author
Goličnik, Marko
author
Mascareñas Cid, José Luis
author
Vázquez Sentís, Marco Eugenio
author
2012
The luminescence of a designed peptide equipped with a coordinatively-unsaturated lanthanide complex is modulated by the phosphorylation state of a serine residue in the sequence. While the phosphorylated state is weakly emissive, even in the presence of an external antenna, removal of the phosphate allows coordination of the sensitizer to the metal, yielding a highly emissive supramolecular complex
Pazos, E., Goličnik, M., Mascareñas, J., & Eugenio Vázquez, M. (2012). Detection of phosphorylation states by intermolecular sensitization of lanthanide–peptide conjugates. Chemical Communications, 48(76), 9534. doi: 10.1039/c2cc34958b
1359-7345
http://hdl.handle.net/10347/18486
10.1039/C2CC34958B
1364-548X
Detection of phosphorylation states by intermolecular sensitization of lanthanide–peptide conjugates
oai:minerva.usc.es:10347/154452023-07-10T06:12:59Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Varela Sandá, Iván
author
Faustino, Hélio
author
Díez Martín, Elena
author
Iglesias Sigüenza, Francisco Javier
author
Grande-Carmona, Francisca
author
Fernández, Rosario
author
Lassaletta, José M.
author
Mascareñas Cid, José Luis
author
López García, Fernando
author
2017-02-22
A straightforward and atom-economical enantioselective approach to highly substituted tetrahydropyrans is reported. The process, which consists of an intermolecular gold-catalyzed [2+2+2] cycloaddition between allenamides, alkenes, and aldehydes, is efficiently catalyzed by both phosphoramidite- and chiral N-heterocyclic carbene-gold catalysts, occurs with complete chemoselectivity and regioselectivity, moderate diastereoselectivity, and moderate to very good enantioselectivities
Varela, Iván, Faustino, Hélio, Díez, Elena, Iglesias-Sigüenza, Javier, Grande-Carmona, Francisca, Fernández, Rosario, Lassaletta, José M., Mascareñas, José L. and López, Fernando, 2017, Gold(I)-Catalyzed Enantioselective [2+2+2] Cycloadditions: An Expedient Entry to Enantioenriched Tetrahydropyran Scaffolds. ACS Catalysis. 2017. Vol. 7, no. 4, p. 2397-2402. DOI 10.1021/acscatal.6b03651. American Chemical Society (ACS)
http://hdl.handle.net/10347/15445
10.1021/acscatal.6b03651
2155-5435
Allenamide
Cycloaddition
Enantioselective synthesis
Gold catalysis
N-heterocyclic carbenes
Tetrahydropyrans
Gold(I)-Catalyzed Enantioselective [2+2+2] Cycloadditions: An Expedient Entry to Enantioenriched Tetrahydropyran Scaffolds
oai:minerva.usc.es:10347/169932023-07-10T06:12:14Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
García, D.
author
Rodríguez-Pérez, L.
author
Herranz, M.A.
author
Peña Gil, Diego
author
Guitián Rivera, Enrique
author
Bailey, S.
author
Al-Galiby, Q.
author
Noori, M.
author
Lambert, C. J.
author
Pérez Meirás, María Dolores
author
Martín, N.
author
2016-04-19
The synthesis of a [60]fullerene-benzyne building block and its further chemical cycloaddition reaction with graphene has resulted in a new all-carbon hybrid material which has been characterized by TGA, FTIR and Raman spectroscopies, XPS as well as AFM and TEM. Based on computational studies, the formation of both [2+2] and [4+2] cycloadducts on the graphene surface is feasible
García, D., Rodríguez-Pérez, L., Herranz, M., Peña, D., Guitián, E., & Bailey, S. et al. (2016). A C60-aryne building block: synthesis of a hybrid all-carbon nanostructure. Chemical Communications, 52(40), 6677-6680. doi: 10.1039/c5cc10462a
1359-7345
http://hdl.handle.net/10347/16993
10.1039/C5CC10462A
1364-548X
A C60-aryne building block: synthesis of a hybrid all-carbon nanostructure
oai:minerva.usc.es:10347/174292023-07-10T06:16:13Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Lostalé Seijo, Irene
author
Montenegro García, Javier
author
2018-09-21
The delivery of nucleic acids with transient activity for genetic engineering is a promising methodology with potential applications in the treatment of diseases ranging from cancer and infectious diseases to heritable disorders. Restoring the expression of a missing protein, correcting defective splicing of transcripts and silencing or modulating the expression of genes are powerful approaches that could have substantial benefits in biological research and medicine. Impressive progress in improving gene delivery has been made in the past decade, and several products have reached the market. However, translating the results of in vitro and preclinical studies into functional therapies is hindered by the suboptimal performance of gene delivery vehicles in capturing, protecting and delivering nucleic acid cargoes safely and efficaciously. Chemistry has a key role in the development of innovative synthetic materials to overcome the challenges of producing next-generation gene delivery therapies and protocols. In this Review, we discuss the latest chemical advances in the production of materials for the delivery of nucleic acids to cells and for gene therapy
Lostalé-Seijo, I., & Montenegro, J. (2018). Synthetic materials at the forefront of gene delivery. Nature Reviews Chemistry, 2(10), 258-277. doi: 10.1038/s41570-018-0039-1
http://hdl.handle.net/10347/17429
10.1038/s41570-018-0039-1
2397-3358
Gene delivery
Gene therapy
Nanoparticles
Synthetic materials at the forefront of gene delivery
oai:minerva.usc.es:10347/125462023-07-10T06:16:24Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Mosquera Mosquera, Jesús
author
Sánchez López, Mateo Isidro
author
Valero, Julián
author
Mendoza, Javier de
author
Vázquez Sentís, Marco Eugenio
author
Mascareñas Cid, José Luis
author
2015-02-18
Conjugation of a short peptide fragment from a bZIP protein to an oligoguanidinium tail results in a DNA-binding miniprotein that selectively interacts with composite sequences containing the peptide-binding site next to an A/T-rich tract. In addition to stabilizing the complex with the target DNA, the oligoguanidinium unit also endows the conjugate with cell internalization properties
Mosquera, J., Sánchez M. I., Valero, J., de Mendoza, J., Vázquez, M. E., Mascareñas, J. L. (2015), Sequence-Selective DNA Binding with Cell-Permeable Oligoguanidinium-Peptide Conjugates. ChemComm., 51, 4811-4814 [doi: 10.1039/C4CC09525A].
1359-7345
E-ISSN 1364-548X
http://hdl.handle.net/10347/12546
10.1039/C4CC09525A
Sequence-selective DNA binding with cell-permeable oligoguanidinium-peptide conjugates
oai:minerva.usc.es:10347/169242023-07-10T06:12:41Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Blanco Rodríguez, Beatriz
author
Sedes, Antía
author
Peón López, Antonio
author
Lamb, Heather
author
Hawkins, Alastair R.
author
Castedo Expósito, José Luis
author
González Bello, Concepción
author
2012-03-05
Several 3-alkylaryl mimics of the enol intermediate in the reaction catalyzed by type II dehydroquinase were synthesized to investigate the effect on the inhibition potency of replacing the oxygen atom in the side chain by a carbon atom. The length and the rigidity of the spacer was also studied. The inhibitory properties of the reported compounds against type II dehydroquinase from Mycobacterium tuberculosis and Helicobacter pylori are also reported. The binding modes of these analogs in the active site of both enzymes were studied by molecular docking using GOLD 5.0 and dynamic simulations studies
Blanco, B., Sedes, A., Peón, A., Lamb, H., Hawkins, A., Castedo, L., & González-Bello, C. (2012). Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency. Organic & Biomolecular Chemistry, 10(18), 3662. doi: 10.1039/c2ob07081b
1477-0520
http://hdl.handle.net/10347/16924
10.1039/C2OB07081B
1477-0539
Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency
oai:minerva.usc.es:10347/243062023-07-10T06:21:35Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Sulleiro, M. V.
author
Quiroga Fernández, Sabela
author
Peña Gil, Diego
author
Pérez Meirás, María Dolores
author
Guitián Rivera, Enrique Carlos
author
Criado Fernández, Alejandro
author
Prato, Maurizio
author
2018
A non-conventional modification of exfoliated few-layer graphene (FLG) with different arynes under microwave (MW) irradiation and solvent-free conditions is reported. The described approach allows reaching fast, efficient and mild covalent functionalization of FLG.
Chem. Commun., 2018,54, 2086-2089
http://hdl.handle.net/10347/24306
10.1039/C7CC08676H
1364-548X
Microwave-induced covalent functionalization of few-layer graphene with arynes under solvent-free conditions
oai:minerva.usc.es:10347/169332023-07-10T06:12:36Zcom_10347_2897com_10347_2890com_10347_2888com_10347_227com_10347_2988com_10347_2889col_10347_12277col_10347_11762
00925njm 22002777a 4500
dc
González Bello, Concepción
author
Tizón, Lorena
author
Lence Quintana, Emilio José
author
Otero Casas, José Manuel
author
Raaij, Mark J. van
author
Martínez Guitián, Marta
author
Beceiro Casas, Alejandro
author
Thompson, Paul
author
Hawkins, Alastair R.
author
2015
The first example of an ammonium derivative that causes a specific modification of the active site of type I dehydroquinase (DHQ1), a dehydratase enzyme that is a promising target for antivirulence drug discovery, is described. The resolution at 1.35 Å of the crystal structure of DHQ1 from Salmonella typhi chemically modified by this ammonium derivative revealed that the ligand is covalently attached to the essential Lys170 through the formation of an amine. The detection by mass spectroscopy of the reaction intermediates, in conjunction with the results of molecular dynamics simulations, allowed us to explain the inhibition mechanism and the experimentally observed differences between S. typhi and Staphylococcus aureus enzymes. The results presented here reveal that the replacement of Phe225 in St-DHQ1 by Tyr214 in Sa-DHQ1 and its hydrogen bonding interaction with the conserved water molecule observed in several crystal structures protects the amino adduct against further dehydration/aromatization reactions. In contrast, for the St-DHQ1 enzyme, the carboxylate group of Asp114, with the assistance of this water molecule, would trigger the formation of a Schiff base that can undergo further dehydration reactions until full aromatization of the cyclohexane ring is achieved. Moreover, in vitro antivirulence studies showed that the reported compound is able to reduce the ability of Salmonella Enteritidis to kill A459 respiratory cells. These studies have identified a good scaffold for the design of irreversible inhibitors that can be used as drugs and has opened up new opportunities for the development of novel antivirulence agents by targeting the DHQ1 enzyme
González-Bello, C., Tizón, L., Lence, E., Otero, J., van Raaij, M., & Martinez-Guitian, M. et al. (2015). Chemical Modification of a Dehydratase Enzyme Involved in Bacterial Virulence by an Ammonium Derivative: Evidence of its Active Site Covalent Adduct. Journal Of The American Chemical Society, 137(29), 9333-9343. doi: 10.1021/jacs.5b04080
0002-7863
http://hdl.handle.net/10347/16933
10.1021/jacs.5b04080
1520-5126
Chemical Modification of a Dehydratase Enzyme Involved in Bacterial Virulence by an Ammonium Derivative: Evidence of its Active Site Covalent Adduct
oai:minerva.usc.es:10347/169532023-07-10T06:12:20Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Liko, Flonja
author
Hindré, François
author
Fernández Megía, Eduardo
author
2016
Radiotherapy is one of the most commonly used cancer treatments, with an estimate of 40% success that could be improved further if more efficient targeting and retention of radiation at the tumor site were achieved. This review focuses on the use of dendrimers in radionanotherapy, an emerging technology aimed to improve the efficiency of radiotherapy by implementing nanovectorization, an already established praxis in drug delivery and diagnosis. The labeling of dendrimers with radionuclides also aims to reduce the dose of radiolabeled materials and, hence, their toxicity and tumor resistance. Examples of radiolabeled dendrimers with alpha, beta, and Auger electron emitters are commented, along with the use of dendrimers in boron neutron capture therapy (BNCT). The conjugation of radiolabeled dendrimers to monoclonal antibodies for a more efficient targeting and the application of dendrimers in gene delivery radiotherapy are also covered
Liko, F., Hindré, F., & Fernandez-Megia, E. (2016). Dendrimers as Innovative Radiopharmaceuticals in Cancer Radionanotherapy. Biomacromolecules, 17(10), 3103-3114. doi: 10.1021/acs.biomac.6b00929
1525-7797
http://hdl.handle.net/10347/16953
10.1021/acs.biomac.6b00929
1526-4602
Dendrimers
Radiomedicine
Radiotherapy
Cancer
Radioimmunotherapy
Dendrimers as Innovative Radiopharmaceuticals in Cancer Radionanotherapy
oai:minerva.usc.es:10347/170052020-06-15T11:50:57Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Pérez-Estrada, S.
author
Sayar, N.
author
Granja Guillán, Juan Ramón
author
2016-10-01
Herein we report the facile construction of taxadiene analogues by ring closing metathesis of dienynes built on a cyclohexenone with a natural configuration at C1 and its further transformation to incorporate most of the key functional groups of taxol
Pérez-Estrada, S.,Sayar, N. & Granja, J. (2017). Towards taxane analogues synthesis by dienyne ring closing metathesis . Org. Chem. Front., 2016,3, 1331-1336 . http://dx.doi.org/10.1039/C6QO00321D
http://hdl.handle.net/10347/17005
10.1039/C6QO00321D
2052-4129
Taxane
Ring closing metathesis
Towards taxane analogues synthesis by dienyne ring closing metathesis
oai:minerva.usc.es:10347/169592023-07-10T06:12:34Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Siebrand, Willem
author
Smedarchina, Zorka
author
Ferro Costas, David
author
Martínez Núñez, Emilio
author
Fernández Ramos, Antonio
author
2018-02-22
In this Reply we answer the two main arguments raised in the Comment. The first argument is related to the binding energy of the methanol dimer and its influence on the dimerization rate constant. We show that the dimerization rate constants calculated in the Comment are unphysically low. We report values that are about two orders of magnitude higher than the values of the Comment, which confirm the conclusions of the original article that dimers can be present in a small amount. The second argument based on the dependence of the pseudo-first order rates on the methanol concentration was already explained in detail in the Supporting Information of the original article
Siebrand, W., Smedarchina, Z., Ferro-Costas, D., Martínez-Núñez, E., & Fernández-Ramos, A. (2018). Reply to the ‘Comment on “Methanol dimer formation drastically enhances hydrogen abstraction from methanol by OH at low temperature”’ by D. Heard, R. Shannon, J. Gomez Martin, R. Caravan, M. Blitz, J. Plane, M. Antiñolo, M. Agundez, E. Jimenez, B. Ballesteros, A. Canosa, G. El Dib, J. Albaladejo and J. Cernicharo, Phys. Chem. Chem. Phys., 2018, 20, DOI: 10.1039/C7CP04561A. Physical Chemistry Chemical Physics, 20(12), 8355-8357. doi: 10.1039/c8cp00519b
1463-9076
http://hdl.handle.net/10347/16959
10.1039/C8CP00519B
1463-9084
Reply to the ‘Comment on “Methanol dimer formation drastically enhances hydrogen abstraction from methanol by OH at low temperature”’ by D. Heard, R. Shannon, J. Gomez Martin, R. Caravan, M. Blitz, J. Plane, M. Antiñolo, M. Agundez, E. Jimenez, B. Ballesteros, A. Canosa, G. El Dib, J. Albaladejo and J. Cernicharo, Phys. Chem. Chem. Phys., 2018, 20, DOI: 10.1039/C7CP04561A
oai:minerva.usc.es:10347/151412023-07-10T06:12:43Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Pazo Pascual, Marta
author
Fernández Caro, Héctor
author
Priegue Caamaño, Juan Manuel
author
Lostalé Seijo, Irene
author
Montenegro García, Javier
author
2017-01-25
We here describe the application of oxime bond formation between a peptide scaffold and different aldehydes to modify the transporting capabilities of penetrating peptides. We show that bonds such as oximes offer a great synthetic advantage for the modification of the properties of model penetrating peptides. We believe that this approach will allow the development of improved intracellular delivery vehicles
Montenegro, Javier, Pazo, Marta, Fernández-Caro, Héctor, Priegue, Juan and Lostalé-Seijo, Irene, 2017, Tuning the Properties of Penetrating Peptides by Oxime Conjugation. Synlett. 2017. DOI 10.1055/s-0036-1588689. Thieme Publishing Group
0936-5214
http://hdl.handle.net/10347/15141
10.1055/s-0036-1588689
1437-2096
Peptide chemistry
Penetrating peptides
Supramolecular chemistry
Membrane transport
Solid-phase peptide synthesis
Tuning the properties of penetrating peptides by oxime conjugation
oai:minerva.usc.es:10347/169092020-01-31T07:46:13Zcom_10347_2988com_10347_2889com_10347_227com_10347_2925com_10347_2891com_10347_2888col_10347_11762col_10347_9937
00925njm 22002777a 4500
dc
Alves, Tiago Vinicius
author
Simón-Carballido, Luis
author
Rei Ornellas, Fernando
author
Fernández-Ramos, Antonio
author
2016-02-29
In this work we present a novel application of the two-dimensional non-separable (2D-NS) method to the calculation of torsional tunneling splittings in systems with two hindered internal rotors. This method could be considered an extension of one-dimensional methods for the case of compounds with two tops. The 2D-NS method includes coupling between torsions in the kinetic and potential energy. Specifically, it has been applied to benzyl alcohol (BA) and two of its fluorine derivatives: 3-fluorobenzyl alcohol (3FBA) and 4-fluorobenzyl alcohol (4FBA). These molecules present two torsions, i.e., about the –CH2OH (ϕ1) and –OH (ϕ2) groups. The electronic structure calculations to build the two-dimensional torsional potential energy surface were performed at the DF-LMP2-F12//DF-LMP2/cc-pVQZ level of theory. For BA and 4FBA the calculated ground-state vibrational level splittings are 429 and 453 MHz, respectively, in good agreement with the experimental values of 337.10 and 492.82 MHz, respectively. In these two cases there are four equivalent wells and the tunneling splitting is the result of transitions between the two closer minima along ϕ1. The analysis of the wavefunctions, as well as the previous experimental work on the system, supports this conclusion. For 3FBA the observed ground-state splitting is 0.82 MHz, whereas in this case the calculated value amounts only to 0.02 MHz. The 2D-NS method, through the analysis of the wavefunctions, shows that this tiny tunneling splitting occurs between the two most stable minima of the potential energy surface. Additionally, we predict that the first vibrationally excited tunneling splitting will also be small and exclusively due to the interconversion between the second lowest minima
Alves, T., Simón-Carballido, L., Ornellas, F., & Fernández-Ramos, A. (2016). Hindered rotor tunneling splittings: an application of the two-dimensional non-separable method to benzyl alcohol and two of its fluorine derivatives. Physical Chemistry Chemical Physics, 18(13), 8945-8953. doi: 10.1039/c5cp05307b
1463-9076
http://hdl.handle.net/10347/16909
10.1039/C5CP05307B
1463-9084
Hindered rotor tunneling splittings: an application of the two-dimensional non-separable method to benzyl alcohol and two of its fluorine derivatives
oai:minerva.usc.es:10347/272742021-12-23T03:02:32Zcom_10347_2988com_10347_2889com_10347_227col_10347_11762
00925njm 22002777a 4500
dc
Méndez Ardoy, Alejandro
author
Bergueiro Álvarez, Julián
author
Montenegro García, Javier
author
2021
The self-assembly of peptides and proteins frequently shows structural plasticity depending on subtle alterations. The acquisition of structural data of these peptide assemblies with atomic level precision will be crucial to understand and predict assembled morphologies.
http://hdl.handle.net/10347/27274
The emergence of order: a closer look on peptide assembly and its complexity
oai:minerva.usc.es:10347/303842023-07-10T06:11:05Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Marcos Atanes, Daniel
author
Vidal Vides, Cristian
author
Navo Najera, Claudio Daniel
author
Peccati, Francesca
author
Jiménez Osés, Gonzalo
author
Mascareñas Cid, José Luis
author
2023
Iridium-catalyzed borylations of aromatic C−H bonds are highly attractive transformations because of the diversification possibilities offered by the resulting boronates. These transformations are best carried out using bidentate bipyridine or phenanthroline ligands, and tend to be governed by steric factors, therefore resulting in the competitive functionalization of meta and/or para positions. We have now discovered that a subtle change in the bipyridine ligand, namely, the introduction of a CF3 substituent at position 5, enables a complete change of regioselectivity in the borylation of aromatic amides, allowing the synthesis of a wide variety of ortho-borylated derivatives. Importantly, thorough computational studies suggest that the exquisite regio- and chemoselectivity stems from unusual outer-sphere interactions between the amide group of the substrate and the CF3-substituted aryl ring of the bipyridine ligand
Marcos-Atanes, D., Vidal, C., Navo, C. D., Peccati, F., Jiménez-Osés, G., Mascareñas, J. L., Angew. Chem. Int. Ed. 2023, e202214510; Angew. Chem. 2023, e202214510.
1433-7851
http://hdl.handle.net/10347/30384
10.1002/anie.202214510
1521-3773
Iridium-Catalyzed ortho-Selective Borylation of Aromatic Amides Enabled by 5-Trifluoromethylated Bipyridine Ligands
oai:minerva.usc.es:10347/119672023-07-10T06:16:39Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Mosquera Mosquera, Jesús
author
Rodríguez Villar, Jéssica
author
Vázquez Sentís, Marco Eugenio
author
Mascareñas Cid, José Luis
author
2014-04-24
We report the construction of conjugates between three variants of the helix 3 region of a Q50K engrailed homeodomain and bisbenzamidine minor-groove DNA binders. The hybrid featuring the sequence of the native protein failed to bind to DNA; however, modifications that increased the α-helical folding propensity of the peptide allowed specific DNA binding by a bipartite (major/minor groove) interaction
Mosquera, J., Rodríguez, J., Vázquez, M. E. and Mascareñas, J. L. (2014), Selective DNA-Binding by Designed Bisbenzamidine-Homeodomain Chimeras. ChemBioChem, 15: 1092–1095. doi: 10.1002/cbic.201400079
1439-7633
http://hdl.handle.net/10347/11967
10.1002/cbic.201400079
DNA recognition
Molecular recognition
Oligonucleotides
Peptides
Supramolecular chemistry
Selective DNA-Binding by Designed Bisbenzamidine-Homeodomain Chimeras
oai:minerva.usc.es:10347/222102023-07-10T06:18:27Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Mosquera Mosquera, Jesús
author
Jiménez Balsa, Adrián
author
Dodero, Verónica Isabel
author
Vázquez Sentís, Marco Eugenio
author
Mascareñas Cid, José Luis
author
2013
One of the strategies used by nature to regulate gene expression relies on the stimulicontrolled combination of DNA-binding proteins. This in turn determines the target-binding
site within the genome, and thereby whether a particular gene is activated or repressed. Here
we demonstrate how a designed basic region leucine zipper-based peptide can be directed
towards two different DNA sequences depending on its dimerization arrangement. While the
monomeric peptide is non-functional, a C-terminal metallo-dimer recognizes the natural
ATF/CREB-binding site (50
-ATGA cg TCAT-30
), and a N-terminal disulphide dimer binds
preferentially to the swapped sequence (50
-TCAT cg ATGA-30
). As the dimerization mode can
be efficiently controlled by appropriate external reagents, it is possible to reversibly drive the
peptide to either DNA site in response to such specific inputs. This represents the first
example of a designed molecule that can bind to more than one specific DNA sequence
depending on changes in its environment
Mosquera Mosquera, J., Jimenez Balsa, A., Dodero, V.I., Vázquez Sentís, M.E. y Mascareñas Cid, J.L.(2013). Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides. Nat. commun., vol.4:1874
2041-1723
http://hdl.handle.net/10347/22210
10.1038/ncomms2825
DNA
Synthetic bZIP peptides
Stimuli-responsive selection of target DNA sequences by synthetic bZIP peptides
oai:minerva.usc.es:10347/174082023-07-10T06:16:00Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Fernández Fernández, David
author
Rodrigues, Catarina A. B.
author
Calvelo Souto, Martín
author
Gulías Costa, Moisés
author
Mascareñas Cid, José Luis
author
López García, Fernando
author
2018-07-10
We report an Ir(I)-catalyzed cycloisomerization methodology that provides access to carbocyclic systems bearing exo-alkene moieties from alkynyl-equipped acyclic precursors. The method relies on the C–H activation of olefinic and (hetero)aromatic C(sp2)–H bonds, followed by an exocyclization to a tethered alkyne, and provides interesting cyclic diene products that are amenable of further elaboration. Importantly, DFT calculations suggests that, in contrast to related hydrocarbonations of alkenes in which either migratory insertions or C–C reductive eliminations have been suggested to be rate-determining, in our reactions, the energetic barrier of these steps is lower than that of the previous C–H activation
Fernández, D., Rodrigues, C., Calvelo, M., Gulías, M., Mascareñas, J., & López, F. (2018). Iridium(I)-Catalyzed Intramolecular Cycloisomerization of Enynes: Scope and Mechanistic Course. ACS Catalysis, 8(8), 7397-7402. doi: 10.1021/acscatal.8b02139
http://hdl.handle.net/10347/17408
10.1021/acscatal.8b02139
2155-5435
Catalysis
Cyclization
C−H activation
Hydrocarbonation
Iridium
Iridium(I)-Catalyzed Intramolecular Cycloisomerization of Enynes: Scope and Mechanistic Course
oai:minerva.usc.es:10347/329882024-03-21T09:21:42Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Vilela Góñez, Karen
author
Suárez García, Juan
author
Sardina, F. Javier
author
Pazos, Yolanda
author
Saá, Ángela
author
Martín Pastor, Manuel
author
2023
One-dimensional selective NMR experiments relying on a J-filter element are proposed to isolate specific signals in crowded 1H spectral regions. The J-filter allows the edition or filtering of signals in a region of interest of the spectrum by exploiting the specific values of their 1H-1H coupling constants and certain parameters of protons coupled to them that appear in less congested parts of the spectrum (chemical shifts and coupling constants). The new experiments permitted the isolation of specific peaks of phytosterol components in a sample obtained from a liquid nutraceutical recommended for lowering blood cholesterol levels in regions with complete overlap in the 1H spectrum.
K. V. Góñez, J. S. García, F. J. Sardina, Y. Pazos, Á. Saá, M. Martín−Pastor, J-filter: An experiment to simplify and isolate specific signals in 1H NMR spectra of complex mixtures based on scalar coupling constants. Magn Reson Chem 2023, 61(11), 615. https://doi.org/10.1002/mrc.5396
0749-1581
http://hdl.handle.net/10347/32988
10.1002/mrc.5396
1097-458X
NMR of mixtures
NMR scalar coupling filter
Selective experiment
Signal edition and filtering
J‐filter: An experiment to simplify and isolate specific signals in 1H NMR spectra of complex mixtures based on scalar coupling constants
oai:minerva.usc.es:10347/170012020-01-31T08:49:38Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Leiro, Victoria
author
Garcia, João Pedro
author
Moreno, Pedro M. D.
author
Spencer, Ana Patrícia
author
Fernández Villamarín, Marcos
author
Riguera Vega, Ricardo
author
Fernández Megía, Eduardo
author
Pêgo, Ana Paula
author
2017-07-07
One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited. However, the development of these dendritic nanocarriers is challenging because of the undesired and/or premature degradation observed during their synthesis and/or application. Here, we report new hybrid-biodegradable, biocompatible, non-toxic, and water-soluble azide-terminated PEG–GATGE dendritic block copolymers, based on a gallic acid (GA) core and triethylene glycol (TG) butanoate arms, incorporating ester bonds (E) at the dendritic arms/shell. Their successful functionalization by “click” chemistry with unprotected alkynated amines allowed complexation and delivery of siRNA. The hydrophobic character of the GATGE building unit confers to these hydrolyzable dendritic bionanomaterials a great ability to complex, protect and mediate the cellular internalization of siRNA. Moreover, the localization of the degradation points at the dendritic periphery, close to the complexed siRNA, was found to be important for nucleic acid release from the nanoparticles, rendering a significant improvement of the transfection efficiency compared to their hydrolytically stable PEG–GATG copolymer counterparts. The present study puts forward these biodegradable PEG–dendritic block copolymers not only as suitable vectors for nucleic acids, but also as new avenues for further developments exploring their use in theranostics
Leiro, V., Garcia, J., Moreno, P., Spencer, A., Fernandez-Villamarin, M., & Riguera, R. et al. (2017). Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA. Journal Of Materials Chemistry B, 5(25), 4901-4917. doi: 10.1039/c7tb00279c
2050-750X
http://hdl.handle.net/10347/17001
10.1039/C7TB00279C
2050-7518
Dendrimers
Degradability
Esters
Gene therapy
siRNA
Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA
oai:minerva.usc.es:10347/265922023-07-10T06:11:29Zcom_10347_2988com_10347_2889com_10347_227com_10347_2927com_10347_2891com_10347_2888col_10347_11762col_10347_12292
00925njm 22002777a 4500
dc
Gutiérrez González, Alejandro
author
Destito, Paolo
author
Rodríguez Couceiro, José
author
Pérez González, Cibrán
author
López García, Fernando
author
Mascareñas Cid, José Luis
author
2021
Tailored ruthenium sandwich complexes bearing photoresponsive arene ligands can efficiently promote azide–thioalkyne cycloaddition (RuAtAC) when irradiated with UV light. The reactions can be performed in a bioorthogonal manner in aqueous mixtures containing biological components. The strategy can also be applied for the selective modification of biopolymers, such as DNA or peptides. Importantly, this ruthenium-based technology and the standard copper-catalyzed azide–alkyne cycloaddition (CuAAC) proved to be compatible and mutually orthogonal
A. Gutiérrez-González, P. Destito, J. R. Couceiro, C. Pérez-González, F. López, J. L. Mascareñas, Angew. Chem. Int. Ed. 2021, 60, 16059
1433-7851
http://hdl.handle.net/10347/26592
10.1002/anie.202103645
1521-3773
Biocompatible reactions
Bioorthogonal reactions
Click chemistry
Ruthenium
Thioalkynes
Bioorthogonal Azide–Thioalkyne Cycloaddition Catalyzed by Photoactivatable Ruthenium(II) Complexes
oai:minerva.usc.es:10347/170242023-07-10T06:12:03Zcom_10347_2897com_10347_2890com_10347_2888com_10347_227com_10347_2988com_10347_2889com_10347_2926com_10347_2891com_10347_2927col_10347_12277col_10347_11762col_10347_15773col_10347_12292
00925njm 22002777a 4500
dc
Bouzada, David
author
Salvadó, Iria
author
Barka, Ghofrane
author
Rama, Gustavo
author
Martínez Costas, José Manuel
author
Lorca, Romina
author
Somoza, Álvaro
author
Melle-Franco, Manuel
author
Vázquez Sentís, Marco Eugenio
author
Vázquez López, Miguel
author
2018
A set of Ru(II) metallopeptides containing the dppz ligand has been synthesized using SPPS methods. Fluorescence titration studies show that those metallopeptides featuring an octaarginine tail display a large binding preference for DNA G-quadruplex structures over those lacking it, and also that the interplay between the octoarginine functionalization and the ancillary ligand in the complex has an essential role in the recognition process. Furthermore, the oligoarginine metallopeptides are also efficiently internalized, causing cell death with signs of apoptosis
Bouzada, D., Salvadó, I., Barka, G., Rama, G., Martínez-Costas, J., & Lorca, R. et al. (2018). Selective G-quadruplex binding by oligoarginine-Ru(dppz) metallopeptides. Chemical Communications, 54(6), 658-661. doi: 10.1039/c7cc08286j
1359-7345
http://hdl.handle.net/10347/17024
10.1039/C7CC08286J
1364-548X
Selective G-quadruplex binding by oligoarginine-Ru(dppz) metallopeptides
marc///col_10347_11762/100