Por favor, use este identificador para citar o enlazar este ítem: https://doi.org/10.3390/ijms10125398

Título: Binding of Natural and Synthetic Polyphenols to Human Dihydrofolate Reductase
Fecha de publicación: 18-dic-2009
Editorial: MDPI
Cita bibliográfica: International Journal of Molecular Sciences. Volumen 10. nº12. Páginas 5398-5410
ISSN: 1422-0067
Materias relacionadas: CDU::5 - Ciencias puras y naturales::57 - Biología::577 - Bioquímica. Biología molecular. Biofísica
Palabras clave: Polyphenols
Tea catechins
Dihydrofolate reductase
Enzyme inhibition
Resumen: Dihydrofolate reductase (DHFR) is the subject of intensive investigation since it appears to be the primary target enzyme for antifolate drugs. Fluorescence quenching experiments show that the ester bond-containing tea polyphenols (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) are potent inhibitors of DHFR with dissociation constants (K-D) of 0.9 and 1.8 mu M, respectively, while polyphenols lacking the ester bound gallate moiety [e.g., (-)-epigallocatechin (EGC) and (-)-epicatechin (EC)] did not bind to this enzyme. To avoid stability and bioavailability problems associated with tea catechins we synthesized a methylated derivative of ECG (3-O-(3,4,5-trimethoxybenzoyl)(-)-epicatechin; TMECG), which effectively binds to DHFR (K-D = 2.1 mu M). In alkaline solution, TMECG generates a stable quinone methide product that strongly binds to the enzyme with a K-D of 8.2 nM. Quercetin glucuronides also bind to DHFR but its effective binding was highly dependent of the sugar residue, with quercetin-3-xyloside being the stronger inhibitor of the enzyme with a K-D of 0.6 mu M. The finding that natural polyphenols are good inhibitors of human DHFR could explain the epidemiological data on their prophylactic effects for certain forms of cancer and open a possibility for the use of natural and synthetic polyphenols in cancer chemotherapy.
Autor/es principal/es: Sánchez del Campo Ferrer, Luis
Sáez Ayala, Magalí
Chazarra Parres, Soledad
Cabezas Herrera, Juan
Rodríguez López, José Neptuno
Facultad/Departamentos/Servicios: Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Bioquímica y Biología Molecular A
URI: http://hdl.handle.net/10201/136986
DOI: https://doi.org/10.3390/ijms10125398
Tipo de documento: info:eu-repo/semantics/article
Número páginas / Extensión: 13
Derechos: info:eu-repo/semantics/openAccess
Atribución 4.0 Internacional
Descripción: This is a Published version of the following article, in International Journal of Molecular Sciences. https://doi.org/10.3390/ijms10125398]. It is deposited under the terms of the Creative Commons Attribution-Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Aparece en las colecciones:Artículos: Bioquímica y Biología Molecular "A"

Ficheros en este ítem:
Fichero Descripción TamañoFormato 
ijms 2009.pdf259,47 kBAdobe PDFVista previa

Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons Creative Commons