Conformational preferences of natural and C3-modified epothilones in aqueous solution
Authors: Erdélyi M, Pfeiffer B, Hauenstein K, Fohrer J, Gertsch J, Altmann KH, Carlomagno T
CellNetworks People: Carlomagno Teresa
Journal: J Med Chem. 2008 Mar 13;51(5):1469-73. doi: 10.1021/jm7013452

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.