Abstract
We report the synthesis of (2E,5E)-4-oxoheptadienedioic acid and (2E)-4-oxoheptenedioic acid and evaluation of both diester and diacid analogues as inhibitors of bacterial dihydrodipicolinate synthase. Enzyme kinetic studies allowed the determination of second-order rate constants of inactivation; and substrate co-incubation studies have shown the inhibitors act at the active-site. Mass spectrometric analyses have further explored the enzyme-inhibitor interaction and determined the sites of enzyme alkylation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkylation
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Amino Acid Sequence
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Binding Sites
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Dicarboxylic Acids / chemical synthesis
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Dicarboxylic Acids / chemistry
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Dicarboxylic Acids / metabolism
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Heptanoic Acids / chemical synthesis*
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Heptanoic Acids / chemistry
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Heptanoic Acids / pharmacology*
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Hydro-Lyases / antagonists & inhibitors*
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Hydro-Lyases / metabolism
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Kinetics
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Mass Spectrometry
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Structure-Activity Relationship
Substances
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Dicarboxylic Acids
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Enzyme Inhibitors
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Heptanoic Acids
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Hydro-Lyases
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4-hydroxy-tetrahydrodipicolinate synthase