MEDI 263 |
| An integrated approach to the study of drug-receptor interactions has been applied to adenosine receptors (ARs) and P2Y nucleotide receptors, all of which are G protein-coupled receptors (GPCRs). This approach is based on probing the receptor structure through site-directed mutagenesis and molecular modeling and the rational design of novel synthetic agonist and antagonist ligands. In this manner, receptor subtype selectivity has been increased, and agonists have been converted into partial agonists and antagonists. Current agonist therapy has been limited by side effects due to the wide distribution of a given GPCR. A new approach to engineering of GPCRs, termed neoceptors, has been explored, in which synthetic small molecule agonists (neoligands) are specifically tailored to activate only receptors in which the putative binding sites have been modified. This orthogonal approach to receptor activation, intended for eventual gene therapy, has been demonstrated for A3 and A2A ARs. |
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Murray Goodman Memorial Symposium
8:30 AM-12:05 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Ballroom A, Oral
Division of Medicinal Chemistry |