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Medicinal research reviews

Harnessing allostery: a novel approach to drug discovery.


PMID 24827416

Abstract

Allostery is the most direct and efficient way for regulation of biological macromolecule function, ranging from the control of metabolic mechanisms to signal transduction pathways. Allosteric modulators target to allosteric sites, offering distinct advantages compared to orthosteric ligands that target to active sites, such as greater specificity, reduced side effects, and lower toxicity. Allosteric modulators have therefore drawn increasing attention as potential therapeutic drugs in the design and development of new drugs. In recent years, advancements in our understanding of the fundamental principles underlying allostery, coupled with the exploitation of powerful techniques and methods in the field of allostery, provide unprecedented opportunities to discover allosteric proteins, detect and characterize allosteric sites, design and develop novel efficient allosteric drugs, and recapitulate the universal features of allosteric proteins and allosteric modulators. In the present review, we summarize the recent advances in the repertoire of allostery, with a particular focus on the aforementioned allosteric compounds.

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