A unified and quantitative receptor model for the microtubule binding of paclitaxel and epothilone |
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Authors: | Wang M Xia X Kim Y Hwang D Jansen J M Botta M Liotta D C Snyder J P |
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Affiliation: | Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. |
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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. |
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