Enhanced Metabolic Stability and Protein‐Binding Properties of Artificial α Helices Derived from a Hydrogen‐Bond Surrogate: Application to Bcl‐xL

Abstract

Artificial α helices prepared by the replacement of a hydrogen bond between residues i and i+4 with a carbon–carbon bond can stabilize biologically relevant peptides in helical conformations (1, internal constraint shaded in gray). α Helices based on hydrogen-bond surrogates that mimic Bak BH3 (2, yellow) can bind their expected protein receptor, Bcl-xL (2, green), with high affinity and resist proteolytic degradation.