Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide

被引：434

作者：

Bernal, Federico

Tyler, Andrew F.

Korsmeyer, Stanley J.

Walensky, Loren D. ^{[1
]}

Verdine, Gregory L.

机构：

[1] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA

[2] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2007年 / 129卷 / 09期

关键词：

D O I：

10.1021/ja0693587

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The p53-hDM2 protein interaction is a validated therapeutic target in cancer. We report the synthesis of stabilized alpha-helix of p53 (SAH-p53) compounds that antagonize the p53-hDM2 interaction. We demonstrate that hydrocarbon stapling confers cellular permeability to a p53 peptide that is then capable of modulating transcriptional activity. The lead SAH-p53 compound triggers apoptosis in hDM2-overexpressing cancer cells by reactivating the native p53 signaling pathway. SAH-p53 is the first example of an all-hydrocarbon i, i+7 stabilized peptide that subverts cancer through direct modulation of a transcriptional pathway.

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页码：2456 / +

页数：3

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