biostudies-literatureUnknown13(12)Ballantine RDThe 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.RSC medicinal chemistry1640-1643https://www.ebi.ac.uk/biostudies/studies/S-EPMC9749936biostudies-literatureSynthesis and structure-activity relationship studies of N-terminal analogues of the lipopeptide antibiotics brevicidine and laterocidine.PMC9749936Ballantine RDHoekstra MBann SJMartin NICochrane SAAl Ayed KfalseSynthesis 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. 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.2022-01-01T00:00:00Z2022 Dec2025-04-18T16:30:32.045Z2025-04-07T03:44:02.835ZS-EPMC97499363654543710.1039/d2md00281g