微管蛋白结合紫杉醇构象的评估：C-4至C-3'桥连紫杉醇类似物的合成、生物学及构效关系研究
Evaluation of the tubulin-bound paclitaxel conformation: synthesis, biology, and SAR studies of C-4 to C-3' bridged paclitaxel analogues.
作者信息
Ganesh Thota, Yang Chao, Norris Andrew, Glass Tom, Bane Susan, Ravindra Rudravajhala, Banerjee Abhijit, Metaferia Belhu, Thomas Shala L, Giannakakou Paraskevi, Alcaraz Ana A, Lakdawala Ami S, Snyder James P, Kingston David G I
机构信息
Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
出版信息
J Med Chem. 2007 Feb 22;50(4):713-25. doi: 10.1021/jm061071x. Epub 2007 Jan 31.
Abstract
The important anticancer drug paclitaxel binds to the beta-subunit of the alphabeta-tubulin dimer in the microtubule in a stoichiometric ratio, promoting microtubule polymerization and stability. The conformation of microtubule-bound drug has been the subject of intense study, and various suggestions have been proposed. In previous work we presented experimental and theoretical evidence that paclitaxel adopts a T-shaped conformation when it is bound to tubulin. In this study we report additional experimental data and calculations that delineate the allowable parameters for effective paclitaxel-tubulin interactions.
摘要
重要的抗癌药物紫杉醇以化学计量比与微管中αβ-微管蛋白二聚体的β亚基结合，促进微管聚合和稳定性。与微管结合的药物构象一直是深入研究的主题，并且已经提出了各种建议。在之前的工作中，我们提供了实验和理论证据，表明紫杉醇与微管蛋白结合时采用T形构象。在本研究中，我们报告了额外的实验数据和计算结果，这些数据和计算结果描绘了有效紫杉醇-微管蛋白相互作用的允许参数。
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