Evaluation of the Tubulin-Bound Paclitaxel Conformation: Synthesis, Biology, and SAR Studies of C-4 to C-3‘ Bridged Paclitaxel Analogues
- 31 January 2007
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 50 (4) , 713-725
- https://doi.org/10.1021/jm061071x
Abstract
The important anticancer drug paclitaxel binds to the β-subunit of the αβ-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.Keywords
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