Two new irreversible inhibitors of dihydrodipicolinate synthase: diethyl (E,E)-4-oxo-2,5-heptadienedioate and diethyl (E)-4-oxo-2-heptenedioate

Jennifer J Turner; Jackie P Healy; Renwick C J Dobson; Juliet A Gerrard; Craig A Hutton

doi:10.1016/j.bmcl.2004.12.043

Two new irreversible inhibitors of dihydrodipicolinate synthase: diethyl (E,E)-4-oxo-2,5-heptadienedioate and diethyl (E)-4-oxo-2-heptenedioate

Bioorg Med Chem Lett. 2005 Feb 15;15(4):995-8. doi: 10.1016/j.bmcl.2004.12.043.

Authors

Jennifer J Turner¹, Jackie P Healy, Renwick C J Dobson, Juliet A Gerrard, Craig A Hutton

Affiliation

¹ School of Chemistry, University of Sydney, NSW 2006, Australia.

PMID: 15686899
DOI: 10.1016/j.bmcl.2004.12.043

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Aspartic Acid / analogs & derivatives*
Aspartic Acid / chemistry
Dicarboxylic Acids / chemical synthesis*
Dicarboxylic Acids / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Escherichia coli Proteins / antagonists & inhibitors
Hydro-Lyases / antagonists & inhibitors*
Kinetics
Lysine / biosynthesis
Molecular Mimicry
Pyruvic Acid / chemistry

Substances

Anti-Bacterial Agents
Dicarboxylic Acids
Enzyme Inhibitors
Escherichia coli Proteins
Aspartic Acid
aspartic semialdehyde
Pyruvic Acid
Hydro-Lyases
4-hydroxy-tetrahydrodipicolinate synthase
Lysine