Sun Haiying, Nikolovska-Coleska Zaneta, Yang Chao-Yie, Xu Liang, Liu Meilan, Tomita York, Pan Hongguang, Yoshioka Yoshiko, Krajewski Krzysztof, Roller Peter P, Wang Shaomeng
Departments of Internal Medicine and Medicinal Chemistry and Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA.
J Am Chem Soc. 2004 Dec 29;126(51):16686-7. doi: 10.1021/ja047438+.
A successful structure-based design and synthesis of a class of highly potent conformationally constrained Smac mimetics is described. The most potent compound has a Ki value of 25 nM binding to the XIAP BIR3 protein and is 23 times more potent than natural Smac peptides. These potent Smac mimetics can serve as powerful chemical and pharmacological tools to further elucidate the role of Smac and its cellular binding partners in apoptosis regulation and may be developed as a new class of anti-cancer drugs.
本文描述了一类基于结构的高效构象受限Smac模拟物的成功设计与合成。最有效的化合物与XIAP BIR3蛋白结合的Ki值为25 nM，比天然Smac肽的效力高23倍。这些强效的Smac模拟物可作为强大的化学和药理学工具，以进一步阐明Smac及其细胞结合伴侣在细胞凋亡调控中的作用，并可能开发成为一类新型抗癌药物。
