Journal
PHARMACOLOGICAL RESEARCH
Volume 113, Issue -, Pages 747-753Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2016.05.030
Keywords
Residence time; Melanocortin 4 receptor; Fluorescence anisotropy; G-protein-coupled receptors; Budded baculoviruses; Binding model
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Funding
- Estonian Ministry of Education and Science [IUT20-17]
- European Union through the European Regional Development Fund to the Competence Centre of Health Technologies [EU48695]
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Ligand binding dynamics and the concept of drug-target residence time are essential factors in the development of novel drugs. Conventional ligand binding assays, which usually collect end-point data, do not provide abundant information regarding the ligand binding kinetics. Therefore, novel methods that allow on-line monitoring of ligand binding processes have to be developed and implemented for drug discovery studies. In this study, we provide a short overview of novel possibilities to characterize ligand binding dynamics to different G protein-coupled receptors (GPCRs). Special attention has been paid to the ligand binding to melanocortin 4 receptors and to the development of a fluorescence anisotropy-based assay system using receptors in budded baculovirus particles. It has been shown that ligand binding to melanocortin 4 receptors occurs to tandemly arranged interconnecting ligand binding sites and that the conventional equilibrium usually cannot be achieved in this system. Therefore, the apparent potencies of the same ligand may differ by up to four orders of magnitude, depending on the experimental conditions and the reporter ligand used. (C) 2016 Elsevier Ltd. All rights reserved.
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