Development of Peptidomimetics Targeting IAPs
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- 作者：Sushil K. Sharma ; Christopher Straub and Leigh Zawel
- 关键词：BIR ; cancer ; caspases ; inhibitors of apoptosis protein (IAP) ; peptidomimetics ; protein– ; protein interaction ; Smac/DIABLO
- 刊名：International Journal of Peptide Research and Therapeutics
- 出版年：2006
- 出版时间：March 2006
- 年：2006
- 卷：12
- 期：1
- 页码：21-32
- 全文大小：392 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Life Sciences
Biochemistry
Animal Anatomy, Morphology and Histology
Polymer Sciences - 出版者：Springer Netherlands
- ISSN：1573-3904
文摘
Inhibitor of apoptosis proteins (IAPs) such as XIAP subvert apoptosis by binding and inhibiting caspases. Because occupation of the XIAP BIR3 peptide binding pocket by Smac abolishes the XIAP–caspase 9 interaction, it is a proapoptotic event of great therapeutic interest. An assay for pocket binding was developed based on the displacement of Smac 7-mer from BIR3. Through the physical and biochemical analysis of a variety of peptides, we have determined the minimum sequence required for inhibition of the Smac–BIR3 interaction and detailed the dimensions and topology of the BIR3 peptide binding pocket. This work describes the structure–activity relationship (SAR) for peptide inhibitors of Smac-IAP binding.