Synthetic Inhibitors of Extended Helix–Protein Interactions Based on a Biphenyl 4,4′‐Dicarboxamide Scaffold

Abstract

Abstract Turn Bak : We present rationally designed scaffolds that mimic the spatial projection of the i, i +4, i +7, and i +11 residues of an α‐helix. A library of biphenyl derivatives was shown by competition fluorescence polarization and ITC to mimic Bak and disrupt the Bak/Bcl‐x L protein–protein interaction. 15 N HSQC experiments confirmed that the surface of Bcl‐x L normally occupied by Bak was the target area of our new synthetic inhibitors. magnified image