Two new irreversible inhibitors of dihydrodipicolinate synthase: diethyl (E,E)-4-oxo-2,5-heptadienedioate and diethyl (E)-4-oxo-2-heptenedioate.
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.
Turner
Jennifer J
JJ
School of Chemistry, University of Sydney, NSW 2006, Australia.
Healy
Jackie P
JP
Dobson
Renwick C J
RC
Gerrard
Juliet A
JA
Hutton
Craig A
CA
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
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