John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y Receptors.

ABSTRACT: We establish structure activity relationships of extracellular nucleosides and nucleotides at G protein-coupled receptors (GPCRs), e.g. adenosine receptors (ARs) and P2Y receptors (P2YRs), respectively. We synthesize selective agents for use as pharmacological probes and potential therapeutic agents (e.g. A3AR agonists for neuropathic pain). Detailed structural information derived from the X-ray crystallographic structures within these families enables the design of novel ligands, guides modification of known agonists and antagonists, and helps predict polypharmacology. Structures were recently reported for the P2Y12 receptor (P2Y12R), an anti-thrombotic target. Comparison of agonist-bound and antagonist-bound P2Y12R indicates unprecedented structural plasticity in the outer portions of th

SUBMITTER: Jacobson KA 

PROVIDER: S-EPMC4423517 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature