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A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins

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A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins

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dc.contributor.author Vendrell-Criado, Victoria es_ES
dc.contributor.author González-Bello, Concepción es_ES
dc.contributor.author Miranda Alonso, Miguel Ángel es_ES
dc.contributor.author Jiménez Molero, María Consuelo es_ES
dc.date.accessioned 2020-11-11T04:32:24Z
dc.date.available 2020-11-11T04:32:24Z
dc.date.issued 2018-06-15 es_ES
dc.identifier.issn 1386-1425 es_ES
dc.identifier.uri http://hdl.handle.net/10251/154805
dc.description.abstract [EN] Binding of the inmunodrepresive agent mycophenolate mofetil (MMP) and its pharmacologically active metabolite mycophenolic acid (MPA) to human serum albumin (HSA) and ¿1-acid glycoprotein (HAAG) has been investigated by an integrated approach involving selective excitation of the drug fluorophore, following their UV-A triggered fluorescence and docking studies. The formation of the protein/ligand complexes was evidenced by a dramatic enhancement of the fluorescence intensity and a hypsochromic shift of the emission band. In HSA, competitive studies using oleic acid as site I probe revealed site I as the main binding site of the ligands. Binding constants revealed that the affinity of the active metabolite by HSA is four-fold higher than its proactive form. Moreover, the affinity of MMP by HSA is three-fold higher than by HAAG. Docking studies revealed significant molecular binding differences in the binding of MMP and MPA to sub-domain IIA of HSA (site 1). For MPA, the aromatic moiety would be in close contact to Trp214 with the flexible chain pointing to the other end of the sub-domain; on the contrary, for MMP, the carboxylate group of the chain would be fixed nearby Trp214 through electrostatic interactions with residues Arg218 and Arg222. es_ES
dc.description.sponsorship Financial support from the Spanish Ministry of Economy and Competiveness (CTQ2013-47872-C2-1-P, CTQ2016-78875-P, SAF2016-75638-R), the Xunta de Galicia (Centro singular de investigacion de Galicia accreditation 2016-2019, ED431G/09), the European Union (European Regional Development Fund-ERDF) and the Generalitat Valenciana (PROMETEO/2017/075) is gratefully acknowledged es_ES
dc.language Inglés es_ES
dc.publisher Elsevier es_ES
dc.relation.ispartof Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Drug-protein binding es_ES
dc.subject Docking es_ES
dc.subject Fluorescence es_ES
dc.subject Human serum albumin es_ES
dc.subject Human alpha(1)-acid glycoprotein es_ES
dc.subject.classification QUIMICA ANALITICA es_ES
dc.subject.classification QUIMICA ORGANICA es_ES
dc.title A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1016/j.saa.2018.03.064 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//SAF2016-75638-R/ES/DESARROLLO DE NUEVOS FARMACOS PARA EL TRATAMIENTO DE LAS INFECCIONES BACTERIANAS MULTIRESISTENTES: APROXIMACIONES QUE INCIDEN SOBRE VIABILIDAD, RESISTENCIA Y VIRULENCIA/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/Xunta de Galicia//ED431G%2F09/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//CTQ2013-47872-C2-1-P/ES/METABOLITOS FOTOACTIVOS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//CTQ2016-78875-P/ES/CONTROL SUPRAMOLECULAR DE LA FOTORREACTIVIDAD EN MEDIOS MICROHETEROGENOS BASADOS EN AMINOACIDOS: GELES MOLECULARES Y PROTEINAS TRANSPORTADORAS COMO NANORREACTORES/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEO%2F2017%2F075/ES/Reacciones fotoquímicas de biomoléculas/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Química - Departament de Química es_ES
dc.description.bibliographicCitation Vendrell-Criado, V.; González-Bello, C.; Miranda Alonso, MÁ.; Jiménez Molero, MC. (2018). A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins. Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy. 199:308-314. https://doi.org/10.1016/j.saa.2018.03.064 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1016/j.saa.2018.03.064 es_ES
dc.description.upvformatpinicio 308 es_ES
dc.description.upvformatpfin 314 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 199 es_ES
dc.identifier.pmid 29627615 es_ES
dc.relation.pasarela S\373091 es_ES
dc.contributor.funder Xunta de Galicia es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES


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