Synthesis and evaluation of analogues of S-adenosyl-L-methionine, as inhibitors of the E. coli cyclopropane fatty acid synthase.
Analogues of S-adenosyl-L-methionine were synthesized and evaluated as inhibitors of the purified E. coli cyclopropane fatty acid synthase, a model for M. tuberculosis cyclopropane synthases that are potential targets for antituberculous drugs. Our results show that the presence of the adenosine moiety, in the inhibitor, is required for strong binding, but that the sulfonium charge is less important. The best inhibitors found were S-adenosyl-l-homocysteine and its sulfoxides.
Guérard
Christine
C
UMR 7613 CNRS, Université Pierre et Marie Curie, 4 place Jussieu, F-75252 Paris cedex 05, France.
Bréard
Maud
M
Courtois
Fabienne
F
Drujon
Thierry
T
Ploux
Olivier
O
D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D012436:S-Adenosylmethionine; D008780:Methyltransferases; C019964:cyclopropane synthetase