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Evaluation of the tubulin-bound paclitaxel conformation: synthesis, biology, and SAR studies of C-4 to C-3' bridged paclitaxel analogues.

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.

SUBMITTER: Ganesh T

PROVIDER: S-EPMC2585518 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Evaluation of the tubulin-bound paclitaxel conformation: synthesis, biology, and SAR studies of C-4 to C-3' bridged paclitaxel analogues.

Ganesh Thota T Yang Chao C Norris Andrew A Glass Tom T Bane Susan S Ravindra Rudravajhala R Banerjee Abhijit A Metaferia Belhu B Thomas Shala L SL Giannakakou Paraskevi P Alcaraz Ana A AA Lakdawala Ami S AS Snyder James P JP Kingston David G I DG

Journal of medicinal chemistry 20070131 4

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 ...[more]

PMID: 17263521

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