Rational design of topographical helix mimics as potent inhibitors of protein-protein interactions.

ABSTRACT: Protein-protein interactions encompass large surface areas, but often a handful of key residues dominate the binding energy landscape. Rationally designed small molecule scaffolds that reproduce the relative positioning and disposition of important binding residues, termed "hotspot residues", have been shown to successfully inhibit specific protein complexes. Although this strategy has led to development of novel synthetic inhibitors of protein complexes, often direct mimicry of natural amino acid residues does not lead to potent inhibitors. Experimental screening of focused compound libraries is used to further optimize inhibitors but the number of possible designs that can be efficiently synthesized and experimentally tested in academic settings is limited. We have applied the principles

SUBMITTER: Lao BB 

PROVIDER: S-EPMC4353027 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature