Kinetic Profile of Neuropeptide-Receptor Interactions

Abstract

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.

Keywords: G-protein-coupled receptor; binding kinetics; endogenous ligand; internalization kinetics; neuropeptide; peptide release.