Abstract
Arsinothricin [AST (1)], a new broad-spectrum organoarsenical antibiotic, is a nonproteinogenic analogue of glutamate that effectively inhibits glutamine synthetase. We report the chemical synthesis of an intermediate in the pathway to 1, hydroxyarsinothricin [AST-OH (2)], which can be converted to 1 by enzymatic methylation catalyzed by the ArsM As(III) S-adenosylmethionine methyltransferase. This is the first report of semisynthesis of 1, providing a source of this novel antibiotic that will be required for future clinical trials.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / pharmacology
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Arsenicals / chemical synthesis*
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Arsenicals / pharmacology
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Chromatography, High Pressure Liquid
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Enzyme Inhibitors / pharmacology
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Glutamate-Ammonia Ligase / antagonists & inhibitors
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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S-Adenosylmethionine / antagonists & inhibitors
Substances
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Anti-Bacterial Agents
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Arsenicals
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Enzyme Inhibitors
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arsinothricin
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S-Adenosylmethionine
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Glutamate-Ammonia Ligase