Evaluation of the Tubulin-Bound Paclitaxel Conformation: Synthesis, Biology, and SAR Studies of C-4 to C-3' Bridged Paclitaxel Analogues

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• 作者：Thota Ganesh ; Chao Yang ; Andrew Norris ; Tom Glass ; Susan Bane ; Rudravajhala Ravindra ; Abhijit Banerjee ; Belhu Metaferia ; Shala L. Thomas ; Paraskevi Giannakakou ; Ana A. Alcaraz ; Ami S. Lakdawala ; James
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：February 22, 2007
• 年：2007
• 卷：50
• 期：4
• 页码：713 - 725
• 全文大小：375K
• 年卷期：v.50,no.4(February 22, 2007)
• ISSN：1520-4804

文摘

The important anticancer drug paclitaxel binds to the s/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-subunit of the s/gifchars/alpha.gif" BORDER=0>s/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-tubulin dimer in the microtubulein a stoichiometric ratio, promoting microtubule polymerization and stability. The conformation ofmicrotubule-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-shapedconformation when it is bound to tubulin. In this study we report additional experimental data and calculationsthat delineate the allowable parameters for effective paclitaxel-tubulin interactions.