Sameek Singh; Wenzhi Tian; Zachary C. Severance; Santosh K. Chaudhary; Viktoriya Anokhina; Basudeb Mondal; Rajaiah Pergu; Prashant Singh; Uttam Dhawa; Santanu Singha; Amit Choudhary
Chem. Soc. Rev., 2023, 52, 5485-5515
https://doi.org/10.1039/D2CS00943A

Abstract

Living systems use proximity to regulate biochemical processes. Inspired by this phenomenon, bifunctional modalities that induce proximity have been developed to redirect cellular processes. An emerging example of this class is molecules that induce ubiquitin-dependent proteasomal degradation of a protein of interest, and their initial development sparked a flurry of discovery for other bifunctional modalities. Recent advances in this area include modalities that can change protein phosphorylation, glycosylation, and acetylation states, modulate gene expression, and recruit components of the immune system. In this review, we highlight bifunctional modalities that perform functions other than degradation and have great potential to revolutionize disease treatment, while also serving as important tools in basic research to explore new aspects of biology.