Conformational Preferences of Natural and C3-Modified Epothilones in Aqueous Solution
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- 作者：Má ; té ; Erdé ; lyi ; Bernhard Pfeiffer ; Kurt Hauenstein ; Jö ; rg Fohrer ; Jü ; rg Gertsch ; Karl-Heinz Altmann ; Teresa Carlomagno
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：March 13, 2008
- 年：2008
- 卷：51
- 期：5
- 页码：1469 - 1473
- 全文大小：536K
- 年卷期：v.51,no.5(March 13, 2008)
- ISSN：1520-4804
文摘
The conformational properties of the microtubule-stabilizing agent epothilone A (1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A (1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.