Abstract
Although NMR in fragment-based drug discovery is utilized almost exclusively to evaluate physical binding between molecules, it should be also a powerful tool for biochemical assay, evaluating inhibitory effect of compounds on enzymatic activity. Time-dependent spectral change in real-time monitoring or inhibitor concentration-dependent spectral change after constant-time reaction was processed by factor analysis, by which reaction rate or IC50 value was obtained. Applications to spermidine synthase of Trypanosoma cruzi, which causes Chagas disease, are described.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Chagas Disease / drug therapy
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Cyclohexylamines / chemical synthesis
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Cyclohexylamines / chemistry
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Cyclohexylamines / pharmacology*
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Dose-Response Relationship, Drug
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Drug Discovery*
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Enzyme Activation / drug effects
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular*
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Spermidine Synthase / antagonists & inhibitors*
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Spermidine Synthase / metabolism
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Structure-Activity Relationship
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Time Factors
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Trypanosoma cruzi / enzymology*
Substances
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Cyclohexylamines
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4-methylcyclohexylamine
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Spermidine Synthase