Activating the p53 anti-cancer pathway by targeting the MDM2/MDMX dimer interface with short peptide segments: a computational peptide design experiment

Abstract

Systematic mutation of the I485 and I489 residues of the KEIQLVIKVFI489A peptide leads to 14 mutant peptides that show at least three-fold preferential binding to the MDM2/MDMX interface (ΔΔG ∼ −3.00 kcal mol−1) lower than the KEIQLVIKVFI489A peptide (ΔΔG = −1.02 kcal mol−1).