Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis.
[reaction: see text] The enzyme LpxC (UDP-3-O-[(R)-3-hydroxymyristoyl]-GlcNAc deacetylase) catalyzes the second step of lipid A biosynthesis and is essential for bacterial growth. A GlcNAc-derived hydroxamic acid inhibitor 8 of this enzyme was synthesized using two different routes. Compound 8 exhibits activity toward LpxC enzymes from a wider spectrum of bacterial species than any of the previously reported hydroxamic acid inhibitors.
Li
Xuechen
X
Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Uchiyama
Taketo
T
Raetz
Christian R H
CR
Hindsgaul
Ole
O
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D002241:Carbohydrates / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D008050:Lipid A / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D002241:Carbohydrates; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D006877:Hydroxamic Acids; D008050:Lipid A; D000581:Amidohydrolases; C097307:UDP-3-O-acyl-N-acetylglucosamine deacetylase