Investigating peptide sequence variations for ‘double-click’ stapled p53 peptides

• Main Authors: Lau, Yu Heng, de Andrade, Peterson, Sköld, Niklas, McKenzie, Grahame J., Venkitaraman, Ashok R., Verma, Chandra, Lane, David P., Spring, David R.
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2016
• Subjects: Amino acids; Peptide sequences
• Online Access: https://hdl.handle.net/10356/83841; http://hdl.handle.net/10220/41497
• Institution: Nanyang Technological University

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.