Inhibitors of the bacterial cell wall biosynthesis enzyme MurC.
A series of phosphinate transition-state analogues of the L-alanine adding enzyme (MurC) of bacterial peptidoglycan biosynthesis was prepared and tested as inhibitors of the Escherichia coli enzyme. Compound 4 was identified as a potent inhibitor of MurC from Escherichia coli with an IC(50) of 49nM.
Reck
F
F
Chemistry, Infection Discovery, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA.
Marmor
S
S
Fisher
S
S
Wuonola
M A
MA
D002473:Cell Wall / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism
D004791:Enzyme Inhibitors; D010457:Peptidoglycan; D010453:Peptide Synthases; C023229:UDP-N-acetylmuramoyl-alanine synthetase