G proteins in drug screening: from analysis of receptor-G protein specificity to manipulation of GPCR-mediated signalling pathways.

@article{citeulike:828244, abstract = {Seven transmembrane G protein coupled receptors (7TM GPCRs) represent one of the largest gene familes in the human genome. Because of the size of the GPCR family, their proven history of being valuable targets for small molecule drug design, the fact that the absolute number of GPCRs that are targets for current medicines represents only a small fraction of the total encoded by the human genome, and that ligands for GPCRs do not have to enter the cell to exert their function, it is very likely that GPCRs will remain major targets for the pharmaceutical industry in the foreseeable future. Despite recent evidence indicating that GPCRs can provide information to cells, that does not require activation of G proteins ("signaling at zero G"), most of the GPCRs known to date function via interaction with and activation of heterotrimeric (alphabetagamma) G proteins. Thus, assay systems translating ligand modulation of GPCRs into G protein-dependent intracellular responses are a key component of both basic research and the drug discovery process. This article will review the current knowledge and recent progress in understanding molecular aspects of specific receptor-G protein recognition. It will also highlight how the knowledge generated by such studies can be transformed into assay systems for GPCR drug discovery.}, address = {Institute for Pharmaceutical Biology, Nussallee 6, 53115 Bonn, Germany. Kostenis@uni-bonn.de}, author = {Kostenis, E. }, citeulike-article-id = {828244}, issn = {1381-6128}, journal = {Curr Pharm Des}, keywords = {activation, cterm, drug, ecl2, gpcr, gproteins, pharmacology}, number = {14}, pages = {1703--1715}, posted-at = {2006-09-05 09:59:05}, priority = {4}, title = {G proteins in drug screening: from analysis of receptor-G protein specificity to manipulation of GPCR-mediated signalling pathways.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16712483}, volume = {12}, year = {2006} }

TY - JOUR ID - citeulike:828244 L3 - citeulike-article-id:828244 N2 - Seven transmembrane G protein coupled receptors (7TM GPCRs) represent one of the largest gene familes in the human genome. Because of the size of the GPCR family, their proven history of being valuable targets for small molecule drug design, the fact that the absolute number of GPCRs that are targets for current medicines represents only a small fraction of the total encoded by the human genome, and that ligands for GPCRs do not have to enter the cell to exert their function, it is very likely that GPCRs will remain major targets for the pharmaceutical industry in the foreseeable future. Despite recent evidence indicating that GPCRs can provide information to cells, that does not require activation of G proteins ("signaling at zero G"), most of the GPCRs known to date function via interaction with and activation of heterotrimeric (alphabetagamma) G proteins. Thus, assay systems translating ligand modulation of GPCRs into G protein-dependent intracellular responses are a key component of both basic research and the drug discovery process. This article will review the current knowledge and recent progress in understanding molecular aspects of specific receptor-G protein recognition. It will also highlight how the knowledge generated by such studies can be transformed into assay systems for GPCR drug discovery. IS - 14 JF - Curr Pharm Des SN - 1381-6128 AD - Institute for Pharmaceutical Biology, Nussallee 6, 53115 Bonn, Germany. Kostenis@uni-bonn.de EP - 1715 TI - G proteins in drug screening: from analysis of receptor-G protein specificity to manipulation of GPCR-mediated signalling pathways. VL - 12 SP - 1703 KW - activation KW - cterm KW - drug KW - ecl2 KW - gpcr KW - gproteins KW - pharmacology AU - Kostenis, E PY - 2006/// UR - http://view.ncbi.nlm.nih.gov/pubmed/16712483 ER -