Common Hot Spots in Protein-Activated GPCRs Enable Discovery of New Ligands for Mapping of G-Protein Signalling Pathways (2010-2012)

Proteins and peptides that bind to human G protein-coupled receptors (GPCRs) on cell surfaces are important regulators of cell function. Compounds that compete for these receptors have been developed into blockbuster drugs, but most such GPCRs are under-exploited as drug targets due to uncertainties about their structures, ligand binding sites and intracellular signalling pathways. This project will speed up discovery of compounds that regulate GPCRs by developing and validating a new approach that comparatively matches hot spots shared in GPCRs to common ligand fragments that bind them. New compounds will be profiled using innovative pathway-independent assays to inform on how to selectively regulate G protein signalling pathways in cells