Wist Aislyn D, Gu Lichuan, Riedl Stefan J, Shi Yigong, McLendon George L
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Bioorg Med Chem. 2007 Apr 15;15(8):2935-43. doi: 10.1016/j.bmc.2007.02.010. Epub 2007 Feb 11.
A small series of peptide mimics was designed and synthesized to contain a heterocyclic ring in place of the potentially labile N-terminal peptide bond of the tetrapeptide containing the Smac-XIAP-binding motif. Two Smac mimics were shown to bind to the BIR3 domain of XIAP with moderate affinity and one displayed increased activity in cells relative to the Smac peptides. The structures of BIR3-XIAP in complex with a Smac peptide and a peptide mimic were solved and analyzed to elucidate the structure-activity relationship surrounding the Smac-binding domain within BIR3-XIAP.
设计并合成了一小系列肽模拟物，以包含一个杂环来取代含有Smac-XIAP结合基序的四肽中潜在不稳定的N端肽键。已证明两种Smac模拟物以中等亲和力与XIAP的BIR3结构域结合，并且其中一种相对于Smac肽在细胞中表现出增强的活性。解析并分析了与Smac肽和肽模拟物复合的BIR3-XIAP的结构，以阐明BIR3-XIAP内Smac结合结构域周围的构效关系。
