Study of G protein-coupled receptors dimerization: From bivalent ligands to drug-like small molecules.

Autor: Qian M; School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China; Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: mqian2019@cczu.edu.cn., Sun Z; School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China., Chen X; School of Pharmacy, Changzhou University, Changzhou 213164, Jiangsu, China., Van Calenbergh S; Laboratory for Medicinal Chemistry, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium. Electronic address: serge.vancalenbergh@ugent.be.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2023 Nov; Vol. 140, pp. 106809. Date of Electronic Publication: 2023 Aug 26.
DOI: 10.1016/j.bioorg.2023.106809
Abstrakt: 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.
Competing Interests: 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.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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