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dc.contributor.authorJakubec, Martin
dc.contributor.authorRylandsholm, Fredrik G.
dc.contributor.authorRainsford, Philip
dc.contributor.authorSilk, Mitchell
dc.contributor.authorBril'kov, Maxim
dc.contributor.authorKristoffersen, Tone
dc.contributor.authorJuskewitz, Eric
dc.contributor.authorEricson, Johanna U
dc.contributor.authorSvendsen, John Sigurd Mjøen
dc.date.accessioned2023-08-08T07:34:11Z
dc.date.available2023-08-08T07:34:11Z
dc.date.issued2023-07-20
dc.description.abstractAntimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative E. coli and AMPs is driven by lipopolysaccharides (LPS) that act as kinetic barriers for the binding of AMPs to the bacterial membrane. A combination of SPR and NMR experiments provide evidence suggesting that cationic AMPs first bind to the negatively charged LPS before reaching a binding place in the lipid bilayer. In the event that the initial LPS-binding is too strong (corresponding to a low dissociation rate), the cationic AMPs cannot effectively get from the LPS to the membrane, and their antimicrobial potency will thus be diminished. On the other hand, the AMPs must also be able to effectively interact with the membrane to exert its activity. The ability of the studied cyclic hexapeptides to bind LPS and to translocate into a lipid membrane is related to the nature of the cationic charge (arginine vs. lysine) and to the distribution of hydrophobicity along the molecule (alternating vs. clumped tryptophan).en_US
dc.identifier.citationJakubec, Rylandsholm, Rainsford, Silk, Bril'kov, Kristoffersen, Juskewitz, Ericson, Svendsen. Goldilocks Dilemma: LPS Works Both as the Initial Target and a Barrier for the Antimicrobial Action of Cationic AMPs on E. coli. Biomolecules. 2023en_US
dc.identifier.cristinIDFRIDAID 2164033
dc.identifier.doi10.3390/biom13071155
dc.identifier.issn2218-273X
dc.identifier.urihttps://hdl.handle.net/10037/29759
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.ispartofRylandsholm, F.G. (2024). Structural characterisation and drug-lipid interaction by NMR spectroscopy. (Doctoral thesis). <a href=https://hdl.handle.net/10037/33752>https://hdl.handle.net/10037/33752</a>
dc.relation.journalBiomolecules
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleGoldilocks Dilemma: LPS Works Both as the Initial Target and a Barrier for the Antimicrobial Action of Cationic AMPs on E. colien_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)