title: Synthesis and biochemical evaluation of selective inhibitors of class II fructose bisphosphate aldolases: towards new synthetic antibiotics.
abstract: 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.
authors.affiliation: LCBB-ICMMO, UMR 8182, Université Paris-Sud, Orsay, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Fonvielle
authors.forename: Mathieu
authors.initials: M
authors.lastname: Coinçon
authors.forename: Racha
authors.initials: R
authors.lastname: Daher
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desbenoit
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kosieradzka
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barilone
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Jurgen
authors.initials: J
authors.lastname: Sygusch
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
authors.forename: Michel
authors.initials: M
authors.lastname: Therisod
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005634:Fructose-Bisphosphate Aldolase