Apamin as a template for structure-based rational design of potent peptide activators of p53

Abstract

The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53, and are important molecular targets for anticancer therapy. Grafting four residues critical for MDM2/MDMX binding to the C-terminal α-helix of apamin converts the bee-venom neurotoxin into a novel class of potent p53 activators with potential antitumor activity.