与固定化热休克蛋白 90α（Hsp90α）的相互作用及 Hsp90α 抑制剂的筛选。
Interaction of cepharanthine with immobilized heat shock protein 90α (Hsp90α) and screening of Hsp90α inhibitors.
机构信息
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Nishinomiya 663-8179, Japan.
出版信息
Anal Biochem. 2013 Mar 1;434(1):202-6. doi: 10.1016/j.ab.2012.11.010. Epub 2012 Dec 3.
Abstract
Heat shock protein 90α (Hsp90α) immobilized on aminopropyl silica gels was prepared via the N- or C-terminal, which was termed Hsp90α-NT or Hsp90α-CT, respectively. Binding interactions of biscoclaurine alkaloids (cepharanthine (CEP), berbamine (BBM), isotetrandrine (ITD), and cycleanine (CCN)) with Hsp90α were examined using the Hsp90α-NT or -CT columns by frontal and zonal chromatography studies. The dissociation constants of CEP, BBM, ITD, and CCN to Hsp90α-NT were estimated to be 5.3, 18.6, 46.3, and 159 μM, respectively, by frontal chromatography techniques. Similar results were obtained with the Hsp90α-CT column. These data suggest that these biscoclaurine alkaloids interact with the middle domain of Hsp90α. This was confirmed by demonstrating that CEP competed with endothelial nitric oxide synthase at the middle domain of Hsp90α, where it was shown to have a dissociation constant of 15 nM. Furthermore, the Hsp90α-NT column was applied for preliminary screening of natural Hsp90α inhibitors by zonal chromatography studies.
摘要
热休克蛋白 90α（Hsp90α）通过 N-或 C-末端固定在氨丙基硅胶上，分别称为 Hsp90α-NT 或 Hsp90α-CT。通过前沿和区域色谱研究，使用 Hsp90α-NT 或 -CT 柱检查双稠吡咯啶生物碱（蝙蝠葛碱（CEP）、小檗胺（BBM）、延胡索乙素（ITD）和轮环藤宁（CCN））与 Hsp90α 的结合相互作用。通过前沿色谱技术，CEP、BBM、ITD 和 CCN 与 Hsp90α-NT 的解离常数分别估计为 5.3、18.6、46.3 和 159 μM。使用 Hsp90α-CT 柱也得到了类似的结果。这些数据表明这些双稠吡咯啶生物碱与 Hsp90α 的中间结构域相互作用。通过证明 CEP 在 Hsp90α 的中间结构域与内皮型一氧化氮合酶竞争，证实了这一点，其中 CEP 的解离常数为 15 nM。此外，通过区域色谱研究，Hsp90α-NT 柱用于初步筛选天然 Hsp90α 抑制剂。
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