Synthesis of an analogue of tabtoxinine as a potential inhibitor of D-alanine:D-alanine ligase (ADP forming)

W J Greenlee; J P Springer; A A Patchett

doi:10.1021/jm00121a030

Synthesis of an analogue of tabtoxinine as a potential inhibitor of D-alanine:D-alanine ligase (ADP forming)

J Med Chem. 1989 Jan;32(1):165-70. doi: 10.1021/jm00121a030.

Authors

W J Greenlee¹, J P Springer, A A Patchett

Affiliation

¹ Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.

PMID: 2562853
DOI: 10.1021/jm00121a030

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.

MeSH terms

Azetidines / pharmacology
Chemical Phenomena
Chemistry
Escherichia coli / drug effects
Glutamate-Ammonia Ligase / antagonists & inhibitors
Monobactams / chemical synthesis*
Monobactams / pharmacology
Peptide Synthases / antagonists & inhibitors*
Peptidoglycan / biosynthesis
Staphylococcus aureus / drug effects
Stereoisomerism
Structure-Activity Relationship

Substances

Azetidines
Monobactams
Peptidoglycan
tabtoxinine beta-lactam
Glutamate-Ammonia Ligase
Peptide Synthases
D-alanylalanine synthetase