title: Opportunities for functional selectivity in GPCR antibodies.
abstract: Monoclonal antibodies (mAbs) have been used for decades as tools to probe the biology and pharmacology of receptors in cells and tissues. They are also increasingly being developed for clinical purposes against a broad range of targets, albeit to a lesser extent for G-protein-coupled receptors (GPCRs) relative to other therapeutic targets. Recent pharmacological, structural and biophysical data have provided a great deal of new insight into the molecular details, complexity and regulation of GPCR function. Whereas GPCRs used to be viewed as having either "on" or "off" conformational states, it is now recognized that their structures may be finely tuned by ligands and other interacting proteins, leading to the selective activation of specific signaling pathways. This information coupled with new technologies for the selection of mAbs targeting GPCRs will be increasingly deployed for the development of highly selective mAbs that recognize conformational determinants leading to novel therapeutics.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. dwebb@scripps.edu
authors.forename: David R
authors.initials: DR
authors.lastname: Webb
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
authors.forename: Anke
authors.initials: A
authors.lastname: Kretz-Rommel
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Stevens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000918:Antibody Specificity; D015195:Drug Design; D006801:Humans; D008024:Ligands; D011487:Protein Conformation / Q000187:drug effects; D015202:Protein Engineering / Q000639:trends; D055550:Protein Stability / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D008024:Ligands; D043562:Receptors, G-Protein-Coupled