Abstract
Non-ribosomal peptides (NRPs) are a rich source of antibiotic candidates. However, it was recently discovered that resistance to NRPs can be mediated by d-stereoselective peptidases. The tridecaptins, a class of NRPs that selectively target Gram-negative bacteria, are degraded by the d-peptidase TriF. Through analysis of a solution NMR structure of tridecaptin A1, we have rationally synthesized new cyclic tridecaptin analogues that retain strong antimicrobial activity and are resistant to TriF.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / pharmacology*
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Bacterial Proteins / antagonists & inhibitors*
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Drug Design
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Gram-Negative Bacteria / drug effects
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Lipopeptides / chemical synthesis
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Lipopeptides / pharmacology*
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Paenibacillus polymyxa / enzymology
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Peptides, Cyclic / chemical synthesis
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Peptides, Cyclic / pharmacology*
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / pharmacology*
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Lipopeptides
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Peptides, Cyclic
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Protease Inhibitors