PHOTOPROBE-PEPTIDES FOR THE SYSTEMATIC CHARACTERIZATION OF THE INTERACTIONS OF ANGIOTENSIN II WITH ITS RECEPTOR AT1

摘要

Seven transmembrane domain (TMD) G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and are implicated in various physiopathologies. Approximatively 50 % of all current market drugs act via these receptors, making them privilegeous targets in pharmacotherapy. The rational design of drugs targeting GPCRs requires a molecular-based knowledge of those proteins that may be acquired by identification of ligand-receptor interactions through photoaffinity labelling. This approach allows to directly map the ligand-receptor interface by covalent bonding of the radio-labelled photoprobe ligand within the immediate molecular surroundings of its cognate receptor. This information may then be used in conjunction with computational molecular modeling procedures, based on the X-ray crystallography of bovine rhodopsin, to build and validate homology molecular models of liganded receptors.