title: Towards Gram-negative antivirulence drugs: new inhibitors of HldE kinase.
abstract: Gram-negative bacteria lacking heptoses in their lipopolysaccharide (LPS) display attenuated virulence and increased sensitivity to human serum and to some antibiotics. Thus inhibition of bacterial heptose synthesis represents an attractive target for the development of new antibacterial agents. HldE is a bifunctional enzyme involved in the synthesis of bacterial heptoses. Development of a biochemical assay suitable for high-throughput screening allowed the discovery of inhibitors 1 and 2 of HldE kinase. Study of the structure-activity relationship of this series of inhibitors led to highly potent compounds.
authors.affiliation: MUTABILIS SA, 102 Avenue Gaston Roussel, 93230 Romainville, France. nicolas.desroy@mutabilis.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Desroy
authors.forename: François
authors.initials: F
authors.lastname: Moreau
authors.forename: Sophia
authors.initials: S
authors.lastname: Briet
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Fralliec
authors.forename: Stephanie
authors.initials: S
authors.lastname: Floquet
authors.forename: Lionel
authors.initials: L
authors.lastname: Durant
authors.forename: Vanida
authors.initials: V
authors.lastname: Vongsouthi
authors.forename: Vincent
authors.initials: V
authors.lastname: Gerusz
authors.forename: Alexis
authors.initials: A
authors.lastname: Denis
authors.forename: Sonia
authors.initials: S
authors.lastname: Escaich
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D006539:Heptoses / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D006539:Heptoses; D009097:Multienzyme Complexes; D017853:Phosphotransferases (Alcohol Group Acceptor); C022534:ribokinase; D009713:Nucleotidyltransferases; C445302:D,D heptose 7-phosphate kinase-D,D-heptose 1-phosphate adenylyltransferase, E coli