Abstract

The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the p53 tumor suppressor, directly contributing to the development and progression of many tumors harboring wild type p53. Antagonizing MDM2 and MDMX to activate the p53 pathway has thus become an attractive new strategy for anticancer drug design. Several different classes of MDM2 and MDMX antagonists have been reported, including low molecular weight compounds, small peptides, miniature proteins, and peptidomimetics. This review aims to summarize the latest progress in the design of peptide activators of the p53 tumor suppressor.

Keywords: MDM2, MDMX, p53, D-peptide, peptidomimetics, mini-protein, proteins, helical, Hairpin, H-bonded, Nutlin-3, antagonists, D-enantiomer, hydrophobic