Covalent and Noncovalent Targeting of the Tcf4/β-Catenin Strand Interface with β-Hairpin Mimics

beta-Strands are a fundamental component of protein structure, and these extended peptide regions serve as binding epitopes for numerous protein-protein complexes. However, synthetic mimics that capture the conformation of these epitopes and inhibit selected protein-protein interactions are rare. Here we describe covalent and noncovalent beta-hairpin mimics of an extended strand region mediating the Tcf4/beta-catenin interaction. Our efforts afford a rationally designed lead for an underexplored region of beta-catenin, which has been the subject of numerous ligand discovery campaigns.

Automated summary

The study describes the design of synthetic mimics of beta-strand epitopes and investigates how to inhibit specific protein-protein interactions. This research fills a gap in the study of an underexplored region of beta-catenin.