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Conformational preferences of natural and C3-modified epothilones in aqueous solution
Máté Erdélyi1, Bernhard Pfeiffer, Kurt Hauenstein
1Max-Planck-Institute for Biophysical Chemistry, NMR-Based Structural Biology, Am Fassberg 11, D-37077 Göttingen, Germany.
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.
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