The importance of solvation in the design of ligands targeting membrane proteins

Angel González, Marta Murcia, Bellinda Benhamú, Mercedes Campillo, María L. López-Rodríguez, Leonardo Pardo

Producció científica: Contribució a una revistaArticleRecercaAvaluat per experts

11 Cites (Scopus)


A crucial contribution to the ligand-receptor binding affinity is, in addition to their electrostatic and van der Waals interactions, the desolvation of the ligand. This is of special relevance in membrane proteins because the ligand has to be transferred from the aqueous environment to the transmembrane binding site crevice. Herein we report the synthesis of new serotonin 5-HT 4 receptor antagonists that replace a key carbonyl group by the thiocarbonyl bioisoster. This modification enhances experimental 5-HT 4 receptor binding affinities by as much as 91 times. Free energy perturbation calculations have shown that the significant decrease of the penalty of desolvation, facilitating the entrance of the ligands into the binding site crevice, compensates for the weaker ligand-receptor interaction. © 2011 The Royal Society of Chemistry.
Idioma originalEnglish
Pàgines (de-a)160-164
Estat de la publicacióPublicada - 1 de març 2011


Navegar pels temes de recerca de 'The importance of solvation in the design of ligands targeting membrane proteins'. Junts formen un fingerprint únic.

Com citar-ho