title: Design and synthesis of AApeptides: a new class of peptide mimics.
abstract: 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.
authors.affiliation: Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.
authors.forename: Yaogang
authors.initials: Y
authors.lastname: Hu
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Li
authors.forename: Said M
authors.initials: SM
authors.lastname: Sebti
authors.forename: Jiandong
authors.initials: J
authors.lastname: Chen
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
mesh_terms: D015195:Drug Design; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors
chemical_list: D010455:Peptides; D057786:Peptidomimetics; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2