title: Enhancer and competitive allosteric modulation model for G-protein-coupled receptors.
abstract: 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 A(1) 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.
authors.affiliation: Dipartimento di Medicina Interna, University of Pisa, Via Roma, 67, 56126 Pisa, Italy. daniele2674@yahoo.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Pietra
authors.forename: Alice
authors.initials: A
authors.lastname: Borghini
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Breschi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Bianucci
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D001681:Biological Assay; D003198:Computer Simulation; D007700:Kinetics; D008954:Models, Biological; D011869:Radioligand Assay; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013816:Thermodynamics; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology
chemical_list: D043682:Receptor, Adenosine A1; D043562:Receptors, G-Protein-Coupled; D013876:Thiophenes; C075004:PD 81723