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...
| Autores: | , , , |
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| 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 |
| Sumario: | [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. |
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