DISTINGUISHING AGONISTS, ANTAGONISTS, AND INVERSE AGONISTS USING PWR

摘要

The biophysical consequences of inverse agonist binding to membrane-bound receptors are characterized by PWR (1). An inverse agonist (TMT-Tic) produces membrane thickness, mass density and refractive index anisotropy increases which are similar to, but considerably smaller than, those generated by agonists. Thus, a third conformational state is produced by this ligand, different from those formed by agonists and antagonists, providing a method of distinguishing between agonist, antagonist, and inverse antagonist ligands of membrane-bound receptors, such as G protein-coupled receptors, utilizing PWR.