Abstract
The synthesis and evaluation of two classes of inhibitors for SgTAM, a 4-methylideneimidazole-5-one (MIO) containing tyrosine aminomutase, are described. A mechanism-based strategy was used to design analogs that mimic the substrate or product of the reaction and form covalent interactions with the enzyme through the MIO prosthetic group. The analogs were characterized by measuring inhibition constants and X-ray crystallographic structural analysis of the co-complexes bound to the aminomutase, SgTAM.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Crystallography, X-Ray
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Drug Design*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Epoxy Compounds / chemistry*
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Epoxy Compounds / pharmacology
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Imidazoles / chemistry
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Intramolecular Transferases / antagonists & inhibitors*
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Intramolecular Transferases / chemistry
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Intramolecular Transferases / drug effects
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Molecular Structure
Substances
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4-methylideneimidazole-5-one
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Enzyme Inhibitors
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Epoxy Compounds
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Imidazoles
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Intramolecular Transferases
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tyrosine 2,3-aminomutase