Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction

Hang Yin, Gui In Lee, Soon Park Hyung, Gregory A. Payne, Johanna M. Rodriguez, Said M. Sebti, Andrew D. Hamilton

Research output: Contribution to journalArticlepeer-review

Abstract

(Chemical Equation Presented) HDM2 regulates p53 by binding to its transactivation domain and promoting its ubiquitin-dependent degradation. Crystallographic analysis of the HDM2/p53 complex revealed that three hydrophobic residues (F19, W23, L26) along one face of the p53 helical peptide are essential for binding (see picture). Terphenyl-based antagonists mimic the α-helical region of p53 and disrupt HDM2/p53 complexation.

Original languageEnglish (US)
Pages (from-to)2704-2707
Number of pages4
JournalAngewandte Chemie - International Edition
Volume44
Issue number18
DOIs
StatePublished - Apr 29 2005

Keywords

  • Drug design
  • Helical structures
  • Inhibitors
  • Protein-protein interactions
  • Proteins

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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