1. 1,3-Phenylene bis(ketoacid) derivatives as inhibitors of Escherichia coli dihydrodipicolinate synthase.
- Author
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Boughton BA, Hor L, Gerrard JA, and Hutton CA
- Subjects
- Enzyme Inhibitors chemical synthesis, Escherichia coli Proteins metabolism, Hydro-Lyases metabolism, Keto Acids chemical synthesis, Kinetics, Mass Spectrometry, Enzyme Inhibitors chemistry, Escherichia coli enzymology, Escherichia coli Proteins antagonists & inhibitors, Hydro-Lyases antagonists & inhibitors, Keto Acids chemistry
- Abstract
Dihydrodipicolinate synthase is a key enzyme in the lysine biosynthesis pathway that catalyzes the condensation of pyruvate and aspartate semi-aldehyde. A series of phenolic ketoacid derivatives that mimic the proposed enzymatic intermediate were designed as potential inhibitors of this enzyme and were synthesized from simple precursors. The ketoacid derivatives were shown to act as slow and slow-tight binding inhibitors. Mass spectrometric experiments provided further evidence to support the proposed model of inhibition, demonstrating either an encounter complex or a condensation product for the slow and slow-tight binding inhibitors, respectively., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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