Inhibition of Escherichia coli glucosamine synthetase by novel electrophilic analogues of glutamine--comparison with 6-diazo-5-oxo-norleucine.
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 gamma-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 (k2/Ki) of 3.5 x 10(5) M(-1) min(-1).
Walker
B
B
Division of Biomedicinal Chemistry, School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, Northern Ireland, UK. brian.walker@qub.ac.uk
Brown
M F
MF
Lynas
J F
JF
Martin
S L
SL
McDowell
A
A
Badet
B
B
Hill
A J
AJ
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D003980:Diazooxonorleucine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D005973:Glutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013440:Sulfides
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D013440:Sulfides; D003980:Diazooxonorleucine; D005973:Glutamine; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); C004784:dimethyl sulfide