Journal of Medicinal Chemistry 2008-03-13

Conformational preferences of natural and C3-modified epothilones in aqueous solution.

Máté Erdélyi, Bernhard Pfeiffer, Kurt Hauenstein, Jörg Fohrer, Jürg Gertsch, Karl-Heinz Altmann, Teresa Carlomagno

Index: J. Med. Chem. 51 , 1469-73, (2008)

Full Text: HTML

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.