Rational Design And Synthesis Of Right-Handed D-Sulfono-Gamma-Aapeptide Helical Foldamers As Potent Inhibitors Of Protein-Protein Interactions

Novel unprecedented helical foldamers have been effectively designed and synthesized. The homogeneous right-handed D-sulfono-gamma-AApeptides represent a new generation of unnatural helical peptidomimetics, which have similar folding conformation to alpha-peptides, making them an ideal molecular scaffold to design alpha-helical mimetics. As demonstrated with p53-MDM2 PPI as a model application, the right-handed D-sulfono-gamma-AApeptides reveal much-enhanced binding affinity compared to the p53 peptide. The design of D-sulfono-gamma-AApeptides may provide a new and alternative strategy to modulate protein-protein interactions.