Kinetic Profile of Neuropeptide-Receptor Interactions

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• 作者：Indira Nederpelt¹ ; Julia Bunnik¹ ; Adriaan P. IJzerman¹ ; Laura H. Heitman¹ ; ^{l.h.heitman@lacdr.leidenuniv.nl}
• 关键词：binding kinetics ; endogenous ligand ; G-protein-coupled receptor ; internalization kinetics ; neuropeptide ; peptide release
• 刊名：Trends in Neurosciences
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：39
• 期：12
• 页码：830-839
• 全文大小：1831 K
• 卷排序：39

文摘

Currently, drug discovery focusses only on quantifying pharmacological parameters, sometimes including binding kinetics, of drug candidates. For a complete understanding of a drug's desired binding kinetics, the kinetics of both the target and its endogenous ligands should be considered. This is because the release and binding kinetics of endogenous ligands in addition to receptor internalization rates are significant contributors to drug–target interactions.Here, we discuss the kinetic profile of three neuropeptides and their receptors; gonadotropin-releasing hormone receptor (GnRHR), neuropeptide Y receptors, and corticotropin-releasing factor receptor 1 (CRF1R). These three examples provide new insights into the importance of kinetic profiles which could improve the understanding of desired drug–target binding kinetics and advance drug discovery for various neurological and psychiatric illnesses.