Synthesis and evaluation of analogues of S-adenosyl-L-methionine, as inhibitors of the E. coli cyclopropane fatty acid synthase.

Abstract

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.

• Authors: Christine Guérard, Maud Bréard, Fabienne Courtois, Thierry Drujon, Olivier Ploux
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 14 Issue 7 Pg. 1661-4 (Apr 05 2004) ISSN: 0960-894X [Print] England
• PMID: 15026045 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Escherichia coli Proteins
• S-Adenosylmethionine
• Methyltransferases
• cyclopropane synthetase

Topics

• Drug Evaluation, Preclinical (methods)
• Enzyme Inhibitors (chemical synthesis, metabolism, pharmacology)
• Escherichia coli Proteins (antagonists & inhibitors, metabolism)
• Methyltransferases (antagonists & inhibitors, metabolism)
• S-Adenosylmethionine (chemical synthesis, metabolism, pharmacology)