Document Report Card

ID: ALA1141391

Journal: J Med Chem

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

Authors: Ganesh T, Yang C, Norris A, Glass T, Bane S, Ravindra R, Banerjee A, Metaferia B, Thomas SL, Giannakakou P, Alcaraz AA, Lakdawala AS, Snyder JP, Kingston DG.

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.

CiteXplore: 17263521

DOI: 10.1021/jm061071x