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

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2007 Feb 1

PMID 17263521

Citations 28

Authors

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 P Snyder

David G I Kingston

Affiliations

Soon will be listed here.

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.

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