Conformational preferences of natural and C3-modified epothilones in aqueous solution.
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.
Erdélyi
Máté
M
Max-Planck-Institute for Biophysical Chemistry, NMR-Based Structural Biology, Am Fassberg 11, D-37077 Göttingen, Germany.
Pfeiffer
Bernhard
B
Hauenstein
Kurt
K
Fohrer
Jörg
J
Gertsch
Jürg
J
Altmann
Karl-Heinz
KH
Carlomagno
Teresa
T
D034261:Epothilones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009010:Monte Carlo Method; D012996:Solutions; D014404:Tubulin / Q000737:chemistry; D014867:Water
D034261:Epothilones; D012996:Solutions; D014404:Tubulin; D014867:Water; C093787:epothilone A