Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Madden, Michael M.²  Muppidi, Avinash²  Li, Zhenyu¹  Li, Xiaolong¹  Chen, Jiandong¹  Lin, Qing² 

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA

[2] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA

关键词: Inhibitors;    Protein-protein interaction;    Dipolar cycloaddition;    Cellular uptake;    Stapled peptides;   

DOI  :  10.1016/j.bmcl.2011.01.004

来源: Elsevier

【 摘 要 】

We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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