Synthesis and biochemical evaluation of selective inhibitors of class II fructose bisphosphate aldolases: towards new synthetic antibiotics.
We report the synthesis and biochemical evaluation of selective inhibitors of class II (zinc-dependent) fructose bisphosphate aldolases. The most active compound is a simplified analogue of fructose bisphosphate, bearing a well-positioned metal chelating group. It is a powerful and highly selective competitive inhibitor of isolated class II aldolases. We report crystallographic studies of this inhibitor bound in the active site of the Helicobacter pylori enzyme. The compound also shows activity against Mycobacterium tuberculosis isolates.
Fonvielle
Matthieu
M
LCBB-ICMMO, UMR 8182, Université Paris-Sud, Orsay, France.
Coinçon
Mathieu
M
Daher
Racha
R
Desbenoit
Nicolas
N
Kosieradzka
Katarzyna
K
Barilone
Nathalie
N
Gicquel
Brigitte
B
Sygusch
Jurgen
J
Jackson
Mary
M
Therisod
Michel
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003461:Crystallography; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005634:Fructose-Bisphosphate Aldolase