Abstract
d-Stereoselective peptidases that degrade nonribosomal peptides (NRPs) were recently discovered and could have serious implications for the future of NRPs as antibiotics. Herein, we report chemical modifications that can be used to impart resistance to the d-peptidases BogQ and TriF. New tridecaptin A analogues were synthesized that retain strong antimicrobial activity and have significantly enhanced d-peptidase stability. In vitro assays confirmed that synthetic analogues retain the ability to bind to their cellular receptor, peptidoglycan intermediate lipid II.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / metabolism
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Anti-Bacterial Agents / pharmacology*
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Cysteine / chemistry
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Enzyme Stability
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Escherichia coli / drug effects
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Hydrolysis
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Microbial Sensitivity Tests
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Peptide Hydrolases / chemistry
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Peptide Hydrolases / metabolism*
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Peptides / chemistry*
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Peptides / metabolism*
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Peptides / pharmacology
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Staphylococcus aureus / drug effects
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Uridine Diphosphate N-Acetylmuramic Acid / analogs & derivatives
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Uridine Diphosphate N-Acetylmuramic Acid / metabolism
Substances
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Anti-Bacterial Agents
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Peptides
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Uridine Diphosphate N-Acetylmuramic Acid
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muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol
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tridecaptins
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Peptide Hydrolases
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Cysteine