Design and synthesis of AApeptides: a new class of peptide mimics

A new family of peptide mimics termed 'AApeptides', which are oligomers of N-acylated-N-aminoethyl amino acids, was proposed. The design and efficient synthesis of AApeptides are described. As proof-of-the-concept, we show that AApeptides can inhibit p53/MDM2 protein-protein interaction with significant activity (IC(50)=38 μM) and specificity. Preliminary data also demonstrates that AApeptides are resistant to enzymatic hydrolysis. With the ease of synthesis and diversification, potent bioactivity, and resistance to proteolysis, the development of sequence-specific AApeptides may expand the potential biomedical applications of peptidomimetics.