Inhibition of escherichia coli glucosamine synthetase by novel electrophilic analogues of glutamine—comparison with 6-diazo-5-oxo-norleucine

• Published in: Bioorganic & medicinal chemistry letters 2000-12, Vol.10 (24), p.2795-2798
• Main Authors: Walker, Brian, Brown, Martin F., Lynas, John F., Martin, S.Lorraine, McDowell, Andrew, Badet, Bernard, Hill, Alan J.
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimetabolites, Antineoplastic - pharmacology; Biological and medical sciences; Diazooxonorleucine - pharmacology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Escherichia coli - enzymology; Glutamine - analogs & derivatives; Glutamine - chemical synthesis; Glutamine - pharmacology; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - antagonists & inhibitors; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) - metabolism; Kinetics; Medical sciences; Pharmacology. Drug treatments; Static Electricity; Structure-Activity Relationship; Sulfides
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00565-5

A series of electrophilic glutamine analogues based on 6-diazo-5-oxo-norleucine has been prepared, using novel synthetic routes, and evaluated as inhibitors of Escherichia coli. glucosamine synthetase. The γ-dimethylsulphonium salt analogue of glutamine was found to be one of the most potent inactivators of this enzyme yet reported, with an apparent second order rate constant ( k 2/ K i) of 3.5×10 5 M −1 min −1.