Covalent And Noncovalent Targeting Of The Tcf4/Beta-Catenin Strand Interface With Beta-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.