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 Hamilton

Research output: Contribution to journalArticle

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

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Ubiquitin
Complexation
Degradation
Peptides

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Yin, H., Lee, G. I., Hyung, S. P., Payne, G. A., Rodriguez, J. M., Sebti, S. M., & Hamilton, A. (2005). Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction. Angewandte Chemie - International Edition, 44(18), 2704-2707. https://doi.org/10.1002/anie.200462316

Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction. / Yin, Hang; Lee, Gui In; Hyung, Soon Park; Payne, Gregory A.; Rodriguez, Johanna M.; Sebti, Said M.; Hamilton, Andrew.

In: Angewandte Chemie - International Edition, Vol. 44, No. 18, 29.04.2005, p. 2704-2707.

Research output: Contribution to journalArticle

Yin, Hang ; Lee, Gui In ; Hyung, Soon Park ; Payne, Gregory A. ; Rodriguez, Johanna M. ; Sebti, Said M. ; Hamilton, Andrew. / Terphenyl-based helical mimetics that disrupt the p53/HDM2 interaction. In: Angewandte Chemie - International Edition. 2005 ; Vol. 44, No. 18. pp. 2704-2707.
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