Synthesis and structure-activity relationship studies of N-terminal analogues of the lipopeptide antibiotics brevicidine and laterocidine

The brevicidine and laterocidine family of lipopeptide antibiotics exhibit strong activity against multidrug-resistant Gram-negative bacteria, while showing low propensity to induce resistance. Both peptides feature a branched lipid tail on the N-terminal residue, which for brevicidine is chiral. He...

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Published in:MedChemComm 2022-12, Vol.13 (12), p.164-1643
Main Authors: Ballantine, Ross D, Al Ayed, Karol, Bann, Samantha J, Hoekstra, Michael, Martin, Nathaniel I, Cochrane, Stephen A
Format: Article
Language:English
Subjects:
Antibiotics
Bacteria
Chemistry
Colistin
E coli
Fatty acids
Gram-negative bacteria
Lipids
Multidrug resistance
Peptides
Synthesis
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cited_by cdi_FETCH-LOGICAL-c428t-572661c8925087b667c36f95824a86c9991e771ee4fc5cc89f57bf0a0c7e47b23
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description The brevicidine and laterocidine family of lipopeptide antibiotics exhibit strong activity against multidrug-resistant Gram-negative bacteria, while showing low propensity to induce resistance. Both peptides feature a branched lipid tail on the N-terminal residue, which for brevicidine is chiral. Here, we report the synthesis and biological evaluation of a library of brevicidine and laterocidine analogues wherein the N-terminal lipid is replaced with linear achiral fatty acids. Optimal lipid chain lengths were determined and new analogues with strong activity against colistin-resistant E. coli produced. SAR studies on brevicidine and laterocidine yield new analogues with strong activity against multidrug-resistant Gram-negative bacteria.
doi_str_mv 10.1039/d2md00281g
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source PubMed Central (Open Access); Royal Society of Chemistry:Jisc Collections:Royal Society of Chemistry Read and Publish 2022-2024 (reading list)
subjects Antibiotics
Bacteria
Chemistry
Colistin
E coli
Fatty acids
Gram-negative bacteria
Lipids
Multidrug resistance
Peptides
Synthesis
title Synthesis and structure-activity relationship studies of N-terminal analogues of the lipopeptide antibiotics brevicidine and laterocidine
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