title: Synthesis of an analogue of tabtoxinine as a potential inhibitor of D-alanine:D-alanine ligase (ADP forming).
abstract: 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.
authors.affiliation: Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.
authors.forename: W J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: J P
authors.initials: JP
authors.lastname: Springer
authors.forename: A A
authors.initials: AA
authors.lastname: Patchett
mesh_terms: 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
chemical_list: D001384:Azetidines; D008997:Monobactams; D010457:Peptidoglycan; C051368:tabtoxinine beta-lactam; D005974:Glutamate-Ammonia Ligase; D010453:Peptide Synthases; C019638:D-alanylalanine synthetase