Stapled Peptides with Improved Potency and Specificity That Activate p53
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- 作者：Christopher J. Brown ; Soo T. Quah ; Janice Jong ; Amanda M. Goh ; Poh C. Chiam ; Kian H. Khoo ; Meng L. Choong ; May A. Lee ; Larisa Yurlova ; Kourosh Zolghadr ; Thomas L. Joseph ; Chandra S. Verma ; David P. Lane
- 刊名：ACS Chemical Biology
- 出版年：2013
- 出版时间：March 15, 2013
- 年：2013
- 卷：8
- 期：3
- 页码：506-512
- 全文大小：399K
- 年卷期：v.8,no.3(March 15, 2013)
- ISSN：1554-8937
文摘
By using a phage display derived peptide as an initial template, compounds have been developed that are highly specific against Mdm2/Mdm4. These compounds exhibit greater potency in p53 activation and protein鈥損rotein interaction assays than a compound derived from the p53 wild-type sequence. Unlike Nutlin, a small molecule inhibitor of Mdm2/Mdm4, the phage derived compounds can arrest cells resistant to p53 induced apoptosis over a wide concentration range without cellular toxicity, suggesting they are highly suitable for cyclotherapy.