Synthesis of an analogue of tabtoxinine as a potential inhibitor of D-alanine:D-alanine ligase (ADP forming).
The design and synthesis of a potential inhibitor of D-alanine:D-alanine ligase (ADP forming) (EC 6.3.2.4) are described. This enzyme, which catalyzes the second step in the biosynthesis of bacterial peptidoglycan, is believed to generate D-alanyl phosphate as an enzyme-bound intermediate. With tabtoxinine, a potent inhibitor of glutamine synthetase, as a model, beta-lactams 9R and 9S were synthesized as potential precursors of a D-alanyl phosphate mimic.
Greenlee
W J
WJ
Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.
Springer
J P
JP
Patchett
A A
AA
D001384:Azetidines / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004926:Escherichia coli / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D008997:Monobactams / Q000138:chemical synthesis* / Q000494:pharmacology; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D010457:Peptidoglycan / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001384:Azetidines; D008997:Monobactams; D010457:Peptidoglycan; C051368:tabtoxinine beta-lactam; D005974:Glutamate-Ammonia Ligase; D010453:Peptide Synthases; C019638:D-alanylalanine synthetase