Abstract
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.
Original language | English |
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Pages (from-to) | 1469-73 |
Number of pages | 5 |
Journal | Journal of Medicinal Chemistry |
Volume | 51 |
Issue number | 5 |
DOIs | |
Publication status | Published - 13 Mar 2008 |
Keywords
- Epothilones/chemistry
- Magnetic Resonance Spectroscopy
- Models, Molecular
- Molecular Conformation
- Monte Carlo Method
- Solutions
- Tubulin/chemistry
- Water