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Stapled Peptides with Improved Potency and Specificity That Activate p53

2012; American Chemical Society; Volume: 8; Issue: 3 Linguagem: Inglês

10.1021/cb3005148

1554-8937

Christopher J. Brown, Soo Tng Quah, J.G.Y. de Jong, Amanda M. Goh, Poh Cheang Chiam, Kian Hoe Khoo, Meng Ling Choong, May A. Lee, Larisa Yurlova, Kourosh Zolghadr, Thomas L. Joseph, Chandra Verma, David P. Lane,

Cancer-related Molecular Pathways

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–protein 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.