An -Helix-Mimicking 12,13-Helix: Designed//-Foldamers as Selective Inhibitors of Protein-Protein Interactions

A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein-protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid (tACBC) was used as the key -amino acid component in the design of //-peptides to structurally mimic a native -helix. Suitably functionalized //-peptides assume an -helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type -peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction.