Investigating peptide sequence variations for ‘double-click’ stapled p53 peptides
Lau, Yu Heng
de Andrade, Peterson
McKenzie, Grahame J.
Venkitaraman, Ashok R.
Lane, David P.
Spring, David R.
Date of Issue2014
School of Biological Sciences
Stapling peptides for inhibiting the p53/MDM2 interaction is a promising strategy for developing anti-cancer therapeutic leads. We evaluate double-click stapled peptides formed from p53-based diazidopeptides with different staple positions and azido amino acid side-chain lengths, determining the impact of these variations on MDM2 binding and cellular activity. We also demonstrate a K24R mutation, necessary for cellular activity in hydrocarbon-stapled p53 peptides, is not required for analogous ‘double-click’ peptides.
Organic & Biomolecular Chemistry
© 2014 The Royal Society of Chemistry.