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

被引：208

作者：

Yin, H

Lee, GI

Park, HS

Payne, GA

Rodriguez, JM

Sebti, SM

Hamilton, AD ^{[1
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Univ Florida, Dept Oncol & Biochem, Res Inst, Tampa, FL 33612 USA

[3] Univ Florida, Dept Mol Biol, Tampa, FL 33612 USA

[4] Univ Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33612 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2005年 / 44卷 / 18期

关键词：

drug design; helical structures; inhibitors; protein-protein interactions; proteins;

D O I：

10.1002/anie.200462316

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(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. © 2005 Wiley-VCH Verlag GmbH &, Co. KGaA.

引用

页码：2704 / 2707

页数：4

共 28 条

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