Why p-OMe- and p-Cl-β-Methylphenethylamines Display Distinct Activities upon MAO-B Binding
Cargando...
Archivos
Fecha
2016
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
PUBLIC LIBRARY SCIENCE
Nombre de Curso
Licencia CC
Licencia CC
Resumen
Despite their structural and chemical commonalities, p-chloro-beta-methylphenethylamine and p-methoxy-beta-methylphenethylamine display distinct inhibitory and substrate activities upon MAO-B binding. Density Functional Theory (DFT) quantum chemical calculations reveal that beta-methylation and para-substitution underpin the observed activities sustained by calculated transition state energy barriers, attained conformations and key differences in their interactions in the enzyme's substrate binding site. Although both compounds meet substrate requirements, it is clear that beta-methylation along with the physicochemical features of the para-substituents on the aromatic ring determine the activity of these compounds upon binding to the MAO B-isoform. While data for a larger set of compounds might lend generality to our conclusions, our experimental and theoretical results strongly suggest that the contrasting activities displayed depend on the conformations adopted by these compounds when they bind to the enzyme.
Notas
Indexación: Web of Science
Palabras clave
MONOAMINE-OXIDASE-B, NONCOVALENT INTERACTION REGIONS, CHEMICAL CLUSTER APPROACH, BENZYLAMINE ANALOGS, SELECTIVE-INHIBITION, MAO-B, SUBSTRATE, MODEL, MECHANISMS, RESOLUTION
Citación
PLoS ONE 11 (5)