Study of G protein-coupled receptors dimerization: From bivalent ligands to drug-like small molecules
- PMID:37651896
- DOI: 10.1016/j.bioorg.2023.106809
Study of G protein-coupled receptors dimerization: From bivalent ligands to drug-like small molecules
Abstract
In the past decades an increasing number of studies revealed that G protein-coupled receptors (GPCRs) are capable of forming dimers or even higher-ordered oligomers, which may modulate receptor function and act as potential drug targets. In this review, we briefly summarized the design strategy of bivalent GPCR ligands and mainly focused on how to use them to study and/or detect GPCP dimerization in vitro and in vivo. Bivalent ligands show specific properties relative to their corresponding monomeric ligands because they are able to bind to GPCR homodimers or heterodimers simultaneously. For example, bivalent ligands with optimal length of spacers often exhibited higher binding affinities for dimers compared to that of monomers. Furthermore, bivalent ligands displayed specific signal transduction compared to monovalent ligands. Finally, we give our perspective on targeting GPCR dimers from traditional bivalent ligands to more drug-like small molecules.
Keywords: Bivalent ligands; Drug-like small molecules; G protein-coupled receptors; GPCR dimerization.
Copyright © 2023 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Similar articles
- Class A G-protein-coupled receptor (GPCR) dimers and bivalent ligands.Hiller C, Kühhorn J, Gmeiner P.Hiller C, et al.J Med Chem. 2013 Sep 12;56(17):6542-59. doi: 10.1021/jm4004335. Epub 2013 Jun 4.J Med Chem. 2013.PMID:23678887
- Bivalent ligands as specific pharmacological tools for G protein-coupled receptor dimers.Berque-Bestel I, Lezoualc'h F, Jockers R.Berque-Bestel I, et al.Curr Drug Discov Technol. 2008 Dec;5(4):312-8. doi: 10.2174/157016308786733591.Curr Drug Discov Technol. 2008.PMID:19075611Review.
- Design of bivalent ligands targeting putative GPCR dimers.Huang B, St Onge CM, Ma H, Zhang Y.Huang B, et al.Drug Discov Today. 2021 Jan;26(1):189-199. doi: 10.1016/j.drudis.2020.10.006. Epub 2020 Oct 16.Drug Discov Today. 2021.PMID:33075471Free PMC article.Review.
- The transmembrane domains of GPCR dimers as targets for drug development.Cai X, Wang D, Zhang R, Chen Y, Chen J.Cai X, et al.Drug Discov Today. 2023 Jan;28(1):103419. doi: 10.1016/j.drudis.2022.103419. Epub 2022 Oct 26.Drug Discov Today. 2023.PMID:36309194
- Dopamine D2 Receptors Dimers: How can we Pharmacologically Target Them?Carli M, Kolachalam S, Aringhieri S, Rossi M, Giovannini L, Maggio R, Scarselli M.Carli M, et al.Curr Neuropharmacol. 2018 Jan 30;16(2):222-230. doi: 10.2174/1570159X15666170518151127.Curr Neuropharmacol. 2018.PMID:28521704Free PMC article.Review.
Cited by
- Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders.Mitroshina EV, Marasanova EA, Vedunova MV.Mitroshina EV, et al.Int J Mol Sci. 2023 Nov 16;24(22):16416. doi: 10.3390/ijms242216416.Int J Mol Sci. 2023.PMID:38003611Free PMC article.Review.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Miscellaneous