Abstract
A series of sulfamate surrogates of methionyl and isoleucyl adenylate have been investigated as MetRS and IleRS inhibitors by modifications of the sulfamate linker and adenine moieties. The discovery of 2-iodo Ile-NHSO(2)-AMP (58) as a potent Escherichia coli IleRS inhibitor revealed that a significant hydrophobic interaction between the 2-substituent of Ile-NHSO(2)-AMP and the adenine binding site of IleRS provided its high potency to the enzyme.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Indicators and Reagents
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Isoleucine-tRNA Ligase / antagonists & inhibitors*
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Methionine-tRNA Ligase / antagonists & inhibitors*
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Models, Molecular
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Molecular Conformation
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Sulfonamides / chemical synthesis*
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Sulfonamides / pharmacology*
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Sulfonic Acids / chemical synthesis*
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Sulfonic Acids / pharmacology*
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Thermus thermophilus / enzymology
Substances
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Enzyme Inhibitors
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Indicators and Reagents
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Sulfonamides
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Sulfonic Acids
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Methionine-tRNA Ligase
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Isoleucine-tRNA Ligase