Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Biochem Pharmacol. 2013 Jan 15;85(2):147-52. doi: 10.1016/j.bcp.2012.08.021. Epub 2012 Sep 10.
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.
单克隆抗体 (mAbs) 已被广泛应用于数十年，作为研究细胞和组织中受体的生物学和药理学的工具。此外，mAbs 也越来越多地被开发用于临床治疗，针对各种靶点，尽管相对于其他治疗靶点，针对 G 蛋白偶联受体 (GPCR) 的开发程度较低。最近的药理学、结构和生物物理数据为 GPCR 功能的分子细节、复杂性和调控提供了大量新的见解。虽然 GPCR 过去被认为具有“开启”或“关闭”构象状态，但现在人们认识到，它们的结构可能会受到配体和其他相互作用蛋白的精细调节，从而导致特定信号通路的选择性激活。这些信息结合针对 GPCR 选择 mAbs 的新技术，将越来越多地用于开发高度选择性的 mAbs，这些 mAbs 可以识别导致新型治疗方法的构象决定因素。
