NMR and molecular modeling study of the conformations of taxol 2'-acetate in chloroform and aqueous dimethyl sulfoxide solutions.
Taxol 2'-acetate, an analog of the antitumor drug taxol, displays no significant in vitro microtubule polymerization activity, thus underscoring the importance of a free 2'-OH group to the biological activity of taxol. Previous work had suggested that the inactivity of taxol 2'-acetate is not due to steric interference by the acetyl group. The present study examined the conformations of taxol 2'-acetate in deuteriochloroform and (2)H2O-deuteriodimethyl sulfoxide solutions and found them to be essentially the same as the respective conformations adopted by taxol itself. Thus, neither destabilization of an active taxol conformation by the acetyl group nor the formation of an important taxol conformation determining role for the 2'-OH group appears likely. The implication of these findings is that the taxol 2'-OH group interacts directly with a protein residue in the taxol-microtubule complex, perhaps as a hydrogen bond donor.
Williams
H J
HJ
Center for Biological NMR, Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255, USA.
Moyna
G
G
Scott
A I
AI
Swindell
C S
CS
Chirlian
L E
LE
Heerding
J M
JM
Williams
D K
DK
D000085:Acetates / Q000737:chemistry / Q000494:pharmacology; D000470:Alkaloids / Q000737:chemistry*; D002725:Chloroform / Q000737:chemistry*; D003903:Deuterium; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D000077143:Docetaxel; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008870:Microtubules / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D043823:Taxoids
D000085:Acetates; D000470:Alkaloids; D043823:Taxoids; D000077143:Docetaxel; D002725:Chloroform; C043188:2'-acetyltaxol; D003903:Deuterium; D017239:Paclitaxel; D004121:Dimethyl Sulfoxide