AI Article Synopsis
- GPCRs can form dimers or oligomers, influencing their function and potential as drug targets.
- Bivalent GPCR ligands can bind to these dimers, offering advantages like increased binding affinity and unique signaling properties compared to regular monomeric ligands.
- The review discusses strategies for designing bivalent ligands and explores the evolution towards more compact, drug-like small molecules for targeting GPCR dimers.
Article 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.
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| http://dx.doi.org/10.1016/j.bioorg.2023.106809 | DOI Listing |
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