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

[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 fluoropho...

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Autores: Vendrell-Criado, Victoria, González-Bello, Concepción, Miranda Alonso, Miguel Ángel, Jiménez, M Consuelo|||0000-0002-8057-4316
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/154805
Acceso en línea:https://riunet.upv.es/handle/10251/154805
Access Level:acceso abierto
Palabra clave:Drug-protein binding
Docking
Fluorescence
Human serum albumin
Human alpha(1)-acid glycoprotein
QUIMICA ANALITICA
QUIMICA ORGANICA
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repository_id_str
spelling A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteinsVendrell-Criado, VictoriaGonzález-Bello, ConcepciónMiranda Alonso, Miguel ÁngelJiménez, M Consuelo|||0000-0002-8057-4316Drug-protein bindingDockingFluorescenceHuman serum albuminHuman alpha(1)-acid glycoproteinQUIMICA ANALITICAQUIMICA ORGANICA[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.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 acknowledgedElsevierDepartamento de QuímicaEscuela Técnica Superior de Ingeniería IndustrialGrupo de estudio de estados excitados: detección, dinámica, transformaciones y campos de aplicaciónXunta de GaliciaGeneralitat ValencianaMinisterio de Economía y CompetitividadRepositorio Institucional de la Universitat Politècnica de València Riunet20182018-06-15journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://riunet.upv.es/handle/10251/154805reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 SAF2016-75638-R DESARROLLO DE NUEVOS FARMACOS PARA EL TRATAMIENTO DE LAS INFECCIONES BACTERIANAS MULTIRESISTENTES: APROXIMACIONES QUE INCIDEN SOBRE VIABILIDAD, RESISTENCIA Y VIRULENCIAXunta de Galicia http://dx.doi.org/10.13039/501100010801 ED431G%2F09Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 CTQ2013-47872-C2-1-P METABOLITOS FOTOACTIVOSMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 CTQ2016-78875-P CONTROL SUPRAMOLECULAR DE LA FOTORREACTIVIDAD EN MEDIOS MICROHETEROGENOS BASADOS EN AMINOACIDOS: GELES MOLECULARES Y PROTEINAS TRANSPORTADORAS COMO NANORREACTORESGeneralitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2017%2F075 Reacciones fotoquímicas de biomoléculasopen accesshttp://purl.org/coar/access_right/c_abf2Reserva de todos los derechoshttp://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/1548052026-06-13T07:49:27Z
dc.title.none.fl_str_mv A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
title A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
spellingShingle A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
Vendrell-Criado, Victoria
Drug-protein binding
Docking
Fluorescence
Human serum albumin
Human alpha(1)-acid glycoprotein
QUIMICA ANALITICA
QUIMICA ORGANICA
title_short A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
title_full A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
title_fullStr A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
title_full_unstemmed A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
title_sort A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins
dc.creator.none.fl_str_mv Vendrell-Criado, Victoria
González-Bello, Concepción
Miranda Alonso, Miguel Ángel
Jiménez, M Consuelo|||0000-0002-8057-4316
author Vendrell-Criado, Victoria
author_facet Vendrell-Criado, Victoria
González-Bello, Concepción
Miranda Alonso, Miguel Ángel
Jiménez, M Consuelo|||0000-0002-8057-4316
author_role author
author2 González-Bello, Concepción
Miranda Alonso, Miguel Ángel
Jiménez, M Consuelo|||0000-0002-8057-4316
author2_role author
author
author
dc.contributor.none.fl_str_mv Departamento de Química
Escuela Técnica Superior de Ingeniería Industrial
Grupo de estudio de estados excitados: detección, dinámica, transformaciones y campos de aplicación
Xunta de Galicia
Generalitat Valenciana
Ministerio de Economía y Competitividad
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Drug-protein binding
Docking
Fluorescence
Human serum albumin
Human alpha(1)-acid glycoprotein
QUIMICA ANALITICA
QUIMICA ORGANICA
topic Drug-protein binding
Docking
Fluorescence
Human serum albumin
Human alpha(1)-acid glycoprotein
QUIMICA ANALITICA
QUIMICA ORGANICA
description [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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-06-15
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://riunet.upv.es/handle/10251/154805
url https://riunet.upv.es/handle/10251/154805
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 SAF2016-75638-R DESARROLLO DE NUEVOS FARMACOS PARA EL TRATAMIENTO DE LAS INFECCIONES BACTERIANAS MULTIRESISTENTES: APROXIMACIONES QUE INCIDEN SOBRE VIABILIDAD, RESISTENCIA Y VIRULENCIA
Xunta de Galicia http://dx.doi.org/10.13039/501100010801 ED431G%2F09
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 CTQ2013-47872-C2-1-P METABOLITOS FOTOACTIVOS
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 CTQ2016-78875-P CONTROL SUPRAMOLECULAR DE LA FOTORREACTIVIDAD EN MEDIOS MICROHETEROGENOS BASADOS EN AMINOACIDOS: GELES MOLECULARES Y PROTEINAS TRANSPORTADORAS COMO NANORREACTORES
Generalitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2017%2F075 Reacciones fotoquímicas de biomoléculas
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reserva de todos los derechos
http://rightsstatements.org/vocab/InC/1.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reserva de todos los derechos
http://rightsstatements.org/vocab/InC/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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