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Org Lett. 1999 Jul 15;1(1):43-6.

A unified and quantitative receptor model for the microtubule binding of paclitaxel and epothilone.

Author information

1
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.

Abstract

[formula: see text] Paclitaxel and epothilone represent the two major classes of antimicrotubule agents that promote tubulin polymerization and, presumably, mitotic arrest during cell division. A common minireceptor binding site model at beta-tubulin has been constructed for these structurally divergent compounds. Utilizing 20 amino acids identified in photoaffinity labeling experiments, the 3-D model correlates measured and predicted Ki's with r = 0.99 and rms(delta Gcalc-delta Gexp) = 0.2 kcal/mol. In addition, the model predicts the affinity of compounds not used in the training set and explains much of the SAR for the paclitaxel and epothilone families.

PMID:
10822530
DOI:
10.1021/ol990521v
[Indexed for MEDLINE]

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