桑沙酰胺A-酰胺的机制研究：一种热休克蛋白90的变构调节剂
Mechanistic studies of Sansalvamide A-amide: an allosteric modulator of Hsp90.
作者信息
Vasko Robert C, Rodriguez Rodrigo A, Cunningham Christian N, Ardi Veronica C, Agard David A, McAlpine Shelli R
机构信息
Department of Chemistry and Biochemistry, 5500 Campanile Road, San Diego State University, San Diego, CA 92182-1030.
出版信息
ACS Med Chem Lett. 2010 Jan 1;1(1):4-8. doi: 10.1021/ml900003t.
Abstract
Herein we show that San A-amide, a structurally unique molecule, influences a subset of cancer-related pathways involving Hsp90. We show that San A-amide specifically binds to the N-middle domain of Hsp90 allosterically disrupts the binding of proteins thought to interact with the Hsp90 C-terminal domain, while having no effect on an N-terminal domain client protein. This unique mechanism suggests that San A-amide is a potential tool for studying C-terminal binding proteins of Hsp90 as well as a promising lead in the development of new cancer therapeutics.
摘要
在此，我们表明San A-酰胺这种结构独特的分子会影响涉及Hsp90的一部分癌症相关通路。我们发现San A-酰胺特异性结合Hsp90的N-中间结构域，变构性地破坏了那些被认为与Hsp90 C-末端结构域相互作用的蛋白质的结合，而对一种N-末端结构域的客户蛋白没有影响。这种独特的机制表明，San A-酰胺是研究Hsp90 C-末端结合蛋白的潜在工具，也是开发新型癌症治疗药物的一个有前景的先导物。
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