Abstract
A novel structural analogue of kynurenine, 2-amino-4-[3'-hydroxyphenyl]-4-hydroxybutanoic acid 6, was synthesised as an inhibitor of kynureninase. The compound had a significant inhibitory effect on kynureninase from both rat and human, giving a K(i) of 100 nM. It was thus found that removal of the aryl amino group coupled with a reduction of the carbonyl group at position 7 of the alanine side chain greatly enhanced potency of the inhibitor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Humans
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Hydrolases / antagonists & inhibitors*
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Hydroxybutyrates / chemical synthesis*
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Hydroxybutyrates / pharmacology*
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Kinetics
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Liver / enzymology
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Phenylbutyrates / chemical synthesis*
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Phenylbutyrates / pharmacology*
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Rats
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Recombinant Proteins / antagonists & inhibitors
Substances
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2-amino-4-(3'-hydroxyphenyl)-4-hydroxybutanoic acid
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Enzyme Inhibitors
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Hydroxybutyrates
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Phenylbutyrates
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Recombinant Proteins
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Hydrolases
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kynureninase