Cell Signalling and Pharmacology Research Group, Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK; Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, UK.
Cell Signalling and Pharmacology Research Group, Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK; Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham and University of Nottingham, Midlands, UK.
Mol Cell Endocrinol. 2019 Apr 5;485:9-19. doi: 10.1016/j.mce.2019.01.018. Epub 2019 Feb 8.
The influence of drug-receptor binding kinetics has often been overlooked during the development of new therapeutics that target G protein-coupled receptors (GPCRs). Over the last decade there has been a growing understanding that an in-depth knowledge of binding kinetics at GPCRs is required to successfully target this class of proteins. Ligand binding to a GPCR is often not a simple single step process with ligand freely diffusing in solution. This review will discuss the experiments and equations that are commonly used to measure binding kinetics and how factors such as allosteric regulation, rebinding and ligand interaction with the plasma membrane may influence these measurements. We will then consider the molecular characteristics of a ligand and if these can be linked to association and dissociation rates.
在开发针对 G 蛋白偶联受体 (GPCR) 的新型治疗药物时，药物-受体结合动力学的影响经常被忽视。在过去的十年中，人们越来越认识到，要成功靶向这一类蛋白质，深入了解 GPCR 上的结合动力学是必需的。配体与 GPCR 的结合通常不是一个简单的自由扩散于溶液中的单一步骤过程。这篇综述将讨论常用于测量结合动力学的实验和方程，以及变构调节、再结合和配体与质膜相互作用等因素如何影响这些测量。然后，我们将考虑配体的分子特征，以及这些特征是否可以与结合和解离速率相关联。
