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Review
. 2022 Jul 14:13:843770.
doi: 10.3389/fendo.2022.843770. eCollection 2022.

Probing GPCR Dimerization Using Peptides

Zara Farooq  1   2 , Lesley A Howell  2 , Peter J McCormick  1
Affiliations
Review

Probing GPCR Dimerization Using Peptides

Zara Farooq et al. Front Endocrinol (Lausanne). .

Abstract

G protein-coupled receptors (GPCRs) are the largest class of membrane proteins and the most common and extensively studied pharmacological target. Numerous studies over the last decade have confirmed that GPCRs do not only exist and function in their monomeric form but in fact, have the ability to form dimers or higher order oligomers with other GPCRs, as well as other classes of receptors. GPCR oligomers have become increasingly attractive to investigate as they have the ability to modulate the pharmacological responses of the receptors which in turn, could have important functional roles in diseases, such as cancer and several neurological & neuropsychiatric disorders. Despite the growing evidence in the field of GPCR oligomerisation, the lack of structural information, as well as targeting the 'undruggable' protein-protein interactions (PPIs) involved in these complexes, has presented difficulties. Outside the field of GPCRs, targeting PPIs has been widely studied, with a variety of techniques being investigated; from small-molecule inhibitors to disrupting peptides. In this review, we will demonstrate several physiologically relevant GPCR dimers and discuss an array of strategies and techniques that can be employed when targeting these complexes, as well as provide ideas for future development.

Keywords: GPCR (G protein coupled receptor); oligomer; peptides; pharmacology; protein-protein interaction; therapeutics targets.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Size comparison of small molecules, peptides and proteins/biologics as therapeutic agents to target protein-protein interactions (PPIs). Created with BioRender.com.
Figure 2
Figure 2
Example of stapled peptide formation. Created with BioRender.com.
Figure 3
Figure 3
Protein 'hot spots' used to target protein-protein interactions (PPIs). Created with BioRender.com.
See this image and copyright information in PMC

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