Rational design of protein–protein interaction inhibitors

Abstract

Low molecular weight compound competing for the binding of the p53 tumor suppressor to the MDM2 oncoprotein.

Abstract

Protein–protein interactions are at the heart of most physiopathological processes. As such, they have attracted considerable attention for designing drugs of the future. Although initially considered as high-value but difficult to identify, low molecular weight compounds able to selectively and potently modulate protein–protein interactions have recently reached clinical trials. Along with high-throughput screening of compound libraries, combining structural and computational approaches has boosted this formerly minor area of research into a currently tremendously active field. This review highlights the very recent developments in the rational design of protein–protein interaction inhibitors.