Abstract
N,O-Didansyl-L-tyrosine (DDT) represented the starting lead for further development of novel non-substrate-like inhibitors of bacterial thymidylate synthase. The N-dansyl structure modulation led to a submicromolar inhibitor of Lactobacillus casei TS (LcTS), which is highly specific with respect to human TS (hTS). Using molecular dynamics simulation, a binding mode for DDT vs LcTS was predicted, explaining activity and species-specificity along the series.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacteria / enzymology*
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Dansyl Compounds / chemical synthesis
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Dansyl Compounds / chemistry*
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Humans
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Lacticaseibacillus casei / enzymology
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Models, Molecular
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Molecular Conformation
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Protein Binding
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Structure-Activity Relationship
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Substrate Specificity
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Thymidylate Synthase / antagonists & inhibitors*
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Thymidylate Synthase / chemistry*
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Tyrosine / analogs & derivatives*
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Tyrosine / chemical synthesis
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Tyrosine / chemistry*
Substances
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Dansyl Compounds
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N,O-didansyl-L-tyrosine
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Tyrosine
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Thymidylate Synthase