title: Phosphinate inhibitors of UDP-N-acetylmuramoyl-L-alanyl-D-glutamate: L-lysine ligase (MurE).
abstract: The increasing emergence of pathogenic bacterial strains with high resistance to antibiotic therapy has created an urgent need for the development of new antibacterial agents that are directed towards novel targets. We have focused our attention on the Mur ligases (MurC-F), which catalyze the early steps of bacterial peptidoglycan biosynthesis, and which to date represent under-exploited targets for antibacterial drug design. We show that some of our phosphinate inhibitors of UDP-N-acetylmuramoyl-L-alanyl:D-glutamate ligase (MurD) also inhibits UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine ligase (MurE). To obtain new information on their structure-activity relationships, three new, structurally related phosphinates were synthesized and evaluated for inhibition of MurD and MurE.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Strancar
authors.forename: Audrey
authors.initials: A
authors.lastname: Boniface
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D010453:Peptide Synthases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010721:Phosphinic Acids; D010453:Peptide Synthases; C049448:UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-lysine ligase; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase