title: Investigating peptide sequence variations for 'double-click' stapled p53 peptides.
abstract: 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.
authors.affiliation: University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom. spring@ch.cam.ac.uk.
authors.forename: Yu Heng
authors.initials: YH
authors.lastname: Lau
authors.forename: Peterson
authors.initials: P
authors.lastname: de Andrade
authors.forename: Niklas
authors.initials: N
authors.lastname: Sköld
authors.forename: Grahame J
authors.initials: GJ
authors.lastname: McKenzie
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Venkitaraman
authors.forename: Chandra
authors.initials: C
authors.lastname: Verma
authors.forename: David P
authors.initials: DP
authors.lastname: Lane
authors.forename: David R
authors.initials: DR
authors.lastname: Spring
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D057930:Click Chemistry / Q000379:methods*; D005454:Fluorescence Polarization; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
chemical_list: D010455:Peptides; D016159:Tumor Suppressor Protein p53