Abstract
Allosteric modulation is the regulation of a protein by binding of an effector molecule at the proteins allosteric site (a site other than that of the endogenous ligand). Allosteric modulators, by virtue of the fact that they may stabilize different global conformations of a receptor, have the potential to disrupt protein-protein interactions of very large proteins and elicit diverse functional responses. The existence of ligands that allosterically modulate the G protein receptor (GPCR) functions provides both challenges and opportunities for drug development campaigns. A number of therapeutic advantages of allosteric modulators over classic orthosteric ligands were proposed, involving nature of response, improved selectivity and ligand-directed signaling. In this review I discuss various aspects of allosteric modulation of GPCRs, which arise from the interactions of receptors with synthetic or endogenous small molecules, ions, lipids and diverse proteins. Detection and quantification of allosteric modulation will be also addressed. In the conclusion I will present future opportunities and challenges in the development of allosteric modulators as therapeutics.
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Tschammer, N. (2016). Allosteric Modulators of the Class A G Protein Coupled Receptors. In: Böldicke, T. (eds) Protein Targeting Compounds. Advances in Experimental Medicine and Biology, vol 917. Springer, Cham. https://doi.org/10.1007/978-3-319-32805-8_9
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