Deorphanization of G-Protein-Coupled Receptors Export

@incollection{citeulike:4908483, abstract = {G-protein-coupled receptors constitute one of the major families of drug targets. Orphan receptors, for which the ligands and function are still unknown, are an attractive set of future targets for presently unmet medical needs. Screening strategies have been developed over the years in order to identify the natural ligands of these receptors. Natural or chimeric G-proteins that can redirect the natural coupling of receptors toward intracellular calcium release are frequently used. Potential problems include poor expression or trafficking to the cell surface, constitutive activity of the receptors, or the presence of endogenous receptors in the cell types used for functional expression, leading to nonspecific responses. Many orphan receptors characterized over the last 10\ years have been associated with previously known bioactive molecules. However, new and unpredicted biological mediators have also been purified from complex biological sources. A\ few old and recent examples, including nociceptin, chemerin, and the F2L peptide are illustrated. Future challenges for the functional characterization of the remaining orphan receptors include the potential requirement of specific proteins necessary for quality control, trafficking or coupling of specific receptors, the possible formation of obligate heterodimers, and the possibility that some constitutively active receptors may lack ligands or respond only to inverse agonists. Adapted expression and screening strategies will be needed to deal with these issues.}, author = {Parmentier, M. and Detheux, M.}, citeulike-article-id = {4908483}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/2789_2006_008}, citeulike-linkout-1 = {http://www.springerlink.com/content/q714x32085686103}, doi = {10.1007/2789_2006_008}, journal = {GPCRs: From Deorphanization to Lead Structure Identification}, keywords = {deorphanization, gpcr}, pages = {163--186}, posted-at = {2009-06-19 15:50:30}, priority = {0}, title = {Deorphanization of G-Protein-Coupled Receptors}, url = {http://dx.doi.org/10.1007/2789_2006_008}, year = {2007} }

TY - CHAP ID - citeulike:4908483 L3 - citeulike-article-id:4908483 N2 - G-protein-coupled receptors constitute one of the major families of drug targets. Orphan receptors, for which the ligands and function are still unknown, are an attractive set of future targets for presently unmet medical needs. Screening strategies have been developed over the years in order to identify the natural ligands of these receptors. Natural or chimeric G-proteins that can redirect the natural coupling of receptors toward intracellular calcium release are frequently used. Potential problems include poor expression or trafficking to the cell surface, constitutive activity of the receptors, or the presence of endogenous receptors in the cell types used for functional expression, leading to nonspecific responses. Many orphan receptors characterized over the last 10 years have been associated with previously known bioactive molecules. However, new and unpredicted biological mediators have also been purified from complex biological sources. A few old and recent examples, including nociceptin, chemerin, and the F2L peptide are illustrated. Future challenges for the functional characterization of the remaining orphan receptors include the potential requirement of specific proteins necessary for quality control, trafficking or coupling of specific receptors, the possible formation of obligate heterodimers, and the possibility that some constitutively active receptors may lack ligands or respond only to inverse agonists. Adapted expression and screening strategies will be needed to deal with these issues. JF - GPCRs: From Deorphanization to Lead Structure Identification EP - 186 TI - Deorphanization of G-Protein-Coupled Receptors SP - 163 KW - deorphanization KW - gpcr AU - Parmentier, M AU - Detheux, M PY - 2007/// UR - http://dx.doi.org/10.1007/2789_2006_008 ER -