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

doi:10.1002/anie.200462316

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

Chemistry

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	2704-2707
Number of pages	4
Journal	Angewandte Chemie - International Edition
Volume	44
Issue number	18
DOIs	https://doi.org/10.1002/anie.200462316
State	Published - Apr 29 2005

Keywords

Drug design
Helical structures
Inhibitors
Protein-protein interactions
Proteins

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.200462316

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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.",

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AU - Payne, Gregory A.

AU - Rodriguez, Johanna M.

AU - Sebti, Said M.

AU - Hamilton, Andrew D.

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AB - (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.

KW - Drug design

KW - Helical structures

KW - Inhibitors

KW - Protein-protein interactions

KW - Proteins

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

Abstract

Keywords

ASJC Scopus subject areas

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