Non-Peptidic α-Helical Mimetics as Protein-Protein Interaction Inhibitors

Protein-protein interactions play a major role in almost all biological pathways and thus, these interactions have a profound impact on the pathogenesis of diseases. The ability to modulate protein-protein interactions with small molecules is an important and rapidly growing area in the field of medicinal chemistry. One of the most common secondary protein structures that are involved in protein-protein interactions are alpha-helices. Thus, a common approach towards developing inhibitors of protein-protein interactions is to design non-peptidic small molecules that mimic the spatial orientations of the side chains of an alpha-helix. In this review, we will discuss a variety of small molecules including terephenyls, terephthalamides, benzamides, enaminones, benzoylureas, pyridines, imidazoles, thiazoles, pyridazines, piperazines, oxopiperazines and diphenylindanes that have been published from 2005-2010 as small molecule helical mimetics.