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dc.contributor.authorMolins Molina, Oscar
dc.contributor.authorPérez Ruiz, Raúl
dc.contributor.authorLence Quintana, Emilio José
dc.contributor.authorGonzález Bello, Concepción
dc.contributor.authorMiranda, Miguel A.
dc.contributor.authorJiménez, Consuelo M.
dc.date.accessioned2020-04-13T05:58:59Z
dc.date.available2020-04-13T05:58:59Z
dc.date.issued2019
dc.identifier.citationMolins-Molina O, Pérez-Ruiz R, Lence E, González-Bello C, Miranda MA. and Jiménez M.C (2019) Photobinding of Triflusal to Human Serum Albumin Investigated by Fluorescence, Proteomic Analysis, and Computational Studies. Front. Pharmacol. 10:1028. doi: 10.3389/fphar.2019.01028
dc.identifier.urihttp://hdl.handle.net/10347/21313
dc.description.abstractTriflusal is a platelet antiaggregant employed for the treatment and prevention of thromboembolic diseases. After administration, it is biotransformed into its active metabolite, the 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). We present here an investigation on HTB photobinding to human serum albumin (HSA), the most abundant protein in plasma, using an approach that combines fluorescence, MS/MS, and peptide fingerprint analysis as well as theoretical calculations (docking and molecular dynamics simulation studies). The proteomic analysis of HTB/HSA photolysates shows that HTB addition takes place at the ε-amino groups of the Lys137, Lys199, Lys205, Lys351, Lys432, Lys525, Lys541 and Lys545 residues and involves replacement of the trifluoromethyl moiety of HTB with a new amide function. Only Lys199 is located in an internal pocket of the protein, and the remaining modified residues are placed in the external part. Docking and molecular dynamic simulation studies reveal that HTB supramolecular binding to HSA occurs in the “V-cleft” region and that the process is assisted by the presence of Glu/Asp residues in the neighborhood of the external Lys, in agreement with the experimentally observed modifications. In principle, photobinding can occur with other trifluoroaromatic compounds and may be responsible for the appearance of undesired photoallergic side effects
dc.description.sponsorshipWe gratefully acknowledge financial support from the Spanish Government (CTQ2016-78875-P, SAF2016-75638-R, BES-2014- 069404, and RETICS network ARADyAL RD16/0006/0030), the Generalitat Valenciana (PROMETEO/2017/075 and CIDEGENT/2018/044), the Xunta de Galicia [Centro Singular de Investigación de Galicia accreditation 2016–2019 (ED431G/09), ED431B 2018/04 and post-doctoral fellowship to EL], and the European Union (European Regional Development Fund— ERDF). The proteomic analysis was performed in the proteomics facility of SCSIE University of Valencia that belongs to ProteoRed PRB3 and is supported by grant PT17/0019, of the PE I+D+i 2013–2016, funded by ISCIII and ERDF. We are grateful to the Centro de Supercomputación de Galicia (CESGA) for use of the Finis Terrae computer
dc.language.isoeng
dc.publisherFrontiers Media
dc.rightsCopyright © 2019 Molins-Molina, Pérez-Ruiz, Lence, González-Bello, Miranda and Jiménez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectTriflusal metabolite
dc.subjectHuman serum albumin
dc.subjectFluorescence
dc.subjectProteomic analysis
dc.subjectDocking and molecular dynamics
dc.titlePhotobinding of triflusal to human serum albumin investigated by fluorescence, proteomic analysis, and computational studies
dc.typejournal article
dc.identifier.doi10.3389/fphar.2019.01028
dc.relation.publisherversionhttps://doi.org/10.3389/fphar.2019.01028
dc.type.hasVersionVoR
dc.identifier.essn1663-9812
dc.rights.accessRightsopen access
dc.contributor.affiliationUniversidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Química Orgánica
dc.description.peerreviewedSI
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BES-2014-069404/ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75638-R/ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2016-78875-P/ES


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Copyright © 2019 Molins-Molina, Pérez-Ruiz, Lence, González-Bello, Miranda and Jiménez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
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 Copyright © 2019 Molins-Molina, Pérez-Ruiz, Lence, González-Bello, Miranda and Jiménez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms





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