Enhancer and competitive allosteric modulation model for G-protein-coupled receptors

[摘要] A new mathematical model referred to as Enhancer and Competitive Allosteric Modulator (ECAM) model developed with the aim of quantitatively describing the interaction of an allosteric modulator with both enhancer and competitive properties towards G-protein-coupled receptors is described here Model simulations for equilibrium (displacement-like and saturation-like) and kinetic (association and dissociation) binding experiments were performed The results showed the ability of the model to interpret a number of possible ligand-receptor binding behaviors In particular the binding properties of PD81723 an enhancer and competitive allosteric modulator for the adenosine AI receptor were experimentally evaluated by radioligand binding assays and Interpreted by the ECAM model The results also offer a theoretical background enabling the design and optimization of compounds endowed with allosteric enhancer competitive agonist antagonist and inverse agonist properties (C) 2010 Elsevier Ltd All rights reserved

[发布日期] 2010-12-21

[关键词] Ligand-receptor interactions;Allosterism;Drug screening;PD81723