Abstract
As aminoacyl adenylate surrogates, a series of methionyl and isoleucyl phenolic analogues containing bioisosteric linkers mimicking ribose have been investigated. Inhibition of synthesized compounds to the aminoacylation reaction by the corresponding Escherichia coli methionyl-tRNA and isoleucyl-tRNA synthetases indicated that 18 was found to be a potent inhibitor of isoleucyl-tRNA synthetase. A molecular modeling study demonstrated that in 18, isovanillate and hydroxamate served as proper surrogates for adenine and ribose in isoleucyl adenylate, respectively.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine / chemistry
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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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Hydroxamic Acids / chemistry
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Inhibitory Concentration 50
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Isoleucine / analogs & derivatives
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Isoleucine / chemical synthesis
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Isoleucine / pharmacology
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Isoleucine-tRNA Ligase / antagonists & inhibitors*
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Methionine / analogs & derivatives
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Methionine / chemical synthesis
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Methionine / pharmacology
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Methionine-tRNA Ligase / antagonists & inhibitors*
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Models, Molecular
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Ribose / chemistry
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Vanillic Acid / analogs & derivatives*
Substances
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Enzyme Inhibitors
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Hydroxamic Acids
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Isoleucine
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Ribose
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Methionine
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Methionine-tRNA Ligase
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Isoleucine-tRNA Ligase
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Vanillic Acid
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Adenine