Abstract
Lipid II analogues bearing major modifications on the second sugar (GlcNAc) were synthesized and evaluated for their substrate activity toward TGases. Unexpectedly, N-deacetyled lipid II decreased its activity dramatically, and the C4-axial OH lipid II became an inhibitor (IC50 = 8 μM) with an approximately 14-fold increase in binding affinity toward TGase (25 vs. 27).
MeSH terms
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Clostridioides difficile / enzymology*
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Dose-Response Relationship, Drug
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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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Escherichia coli / enzymology*
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Lipids / chemistry
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Lipids / pharmacology*
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Peptidoglycan Glycosyltransferase / antagonists & inhibitors*
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Peptidoglycan Glycosyltransferase / metabolism
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Structure-Activity Relationship
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Substrate Specificity
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Sugars / chemical synthesis
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Sugars / chemistry
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Sugars / pharmacology*
Substances
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Enzyme Inhibitors
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Lipids
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Sugars
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Peptidoglycan Glycosyltransferase