title: Two new irreversible inhibitors of dihydrodipicolinate synthase: diethyl (E,E)-4-oxo-2,5-heptadienedioate and diethyl (E)-4-oxo-2-heptenedioate.
abstract: Dihydrodipicolinate synthase (DHDPS) is a key enzyme in lysine biosynthesis and an important antibiotic target. The enzyme catalyses the condensation of (S)-aspartate semialdehyde (ASA) and pyruvate to form dihydrodipicolinate. Two new irreversible inhibitors of dihydrodipicolinate synthase are reported, designed to mimic the acyclic enzyme-bound condensation product of ASA and pyruvate. These compounds represent an important new lead in the design of potent inhibitors for this enzyme.
authors.affiliation: School of Chemistry, University of Sydney, NSW 2006, Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Turner
authors.forename: Jackie P
authors.initials: JP
authors.lastname: Healy
authors.forename: Renwick C J
authors.initials: RC
authors.lastname: Dobson
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Gerrard
authors.forename: Craig A
authors.initials: CA
authors.lastname: Hutton
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D003998:Dicarboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors; D006836:Hydro-Lyases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008239:Lysine / Q000096:biosynthesis; D018716:Molecular Mimicry; D019289:Pyruvic Acid / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D001224:Aspartic Acid; C006644:aspartic semialdehyde; D019289:Pyruvic Acid; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase; D008239:Lysine