Abstract
Three nonhydrolyzable aspartyl adenylate analogs have been prepared and tested as inhibitors of E. coli aspartyl-tRNA synthetase. 5'-O-[N-(L-Aspartyl)sulfamoyl]adenosine is a potent competitive inhibitor (K(i) = 15 nM) whereas L-aspartol adenylate is a weaker inhibitor (K(i) = 45 microM) with respect to aspartic acid. The corresponding ketomethylphosphonate (a novel isosteric replacement) is also a strong inhibitor (K(i) = 123 nM).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Monophosphate / analogs & derivatives*
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Adenosine Monophosphate / chemical synthesis*
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Adenosine Monophosphate / pharmacology*
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Amino Acyl-tRNA Synthetases / antagonists & inhibitors*
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Aspartic Acid / analogs & derivatives*
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Aspartic Acid / chemical synthesis*
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Aspartic Acid / pharmacology*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Escherichia coli / enzymology
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Magnetic Resonance Spectroscopy
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Spectrometry, Mass, Electrospray Ionization
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Spectrophotometry, Infrared
Substances
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Enzyme Inhibitors
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aspartyl adenylate
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Aspartic Acid
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Adenosine Monophosphate
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Amino Acyl-tRNA Synthetases