A new class of peptide mimics termed “γ-AApeptides” has been described. The design and synthesis of γ-AApeptides, and potential bioactivities towards p53/MDM2 interaction were demonstrated. γ-AApeptides were also found to be highly resistant to proteolysis. The development of sequence-specific γ-AApeptides may lead to a family of peptidomimetics with a new framework for drug discovery or peptide/protein mimicry.