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

  • J Med Chem. 2008 Mar 13;51(5):1469-73. doi: 10.1021/jm7013452.
Máté Erdélyi  1 ,  Bernhard Pfeiffer ,  Kurt Hauenstein ,  Jörg Fohrer ,  Jürg Gertsch ,  Karl-Heinz Altmann ,  Teresa Carlomagno
Affiliations
  • 1. Max-Planck-Institute for Biophysical Chemistry, NMR-Based Structural Biology, Am Fassberg 11, D-37077 Göttingen, Germany.
PMID: 18271516 DOI: 10.1021/jm7013452
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.