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.

中文翻译：

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开发靶向 IAP 的肽模拟物。

细胞凋亡蛋白 (IAP) 抑制剂如 XIAP 通过结合和抑制半胱天冬酶来破坏细胞凋亡。由于 Smac 占据 XIAP BIR3 肽结合口袋会消除 XIAP-半胱天冬酶 9 相互作用，因此这是一个具有重要治疗意义的促凋亡事件。基于 Smac 7-mer 从 BIR3 的置换开发了一种口袋结合分析。通过对多种肽的物理和生化分析，我们确定了抑制 Smac-BIR3 相互作用所需的最小序列，并详细说明了 BIR3 肽结合口袋的尺寸和拓扑结构。这项工作描述了 Smac-IAP 结合的肽抑制剂的构效关系 (SAR)。