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Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K

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cris.lastimport.scopus2024-02-12T20:44:19Z
dc.abstract.enGiven the widespread demand for novel antibacterial agents, we modified a cell-penetrating peptide (KFF)3K to transform it into an antibacterial peptide. Namely, we inserted a hydrocarbon staple into the (KFF)3K sequence to induce and stabilize its membrane-active secondary structure. The staples were introduced at two positions, (KFF)3K[5–9] and (KFF)3K[2–6], to retain the initial amphipathic character of the unstapled peptide. The stapled analogues are protease resistant contrary to (KFF)3K; 90% of the stapled (KFF)3K[5–9] peptide remained undigested after incubation in chymotrypsin solution. The stapled peptides showed antibacterial activity (with minimal inhibitory concentrations in the range of 2–16 µM) against various Gram-positive and Gram-negative strains, contrary to unmodified (KFF)3K, which had no antibacterial effect against any strain at concentrations up to 32 µM. Also, both stapled peptides adopted an α-helical structure in the buffer and micellar environment, contrary to a mostly undefined structure of the unstapled (KFF)3K in the buffer. We found that the antibacterial activity of (KFF)3K analogues is related to their disruptive effect on cell membranes and we showed that by stapling this cell-penetrating peptide, we can induce its antibacterial character.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorTrylska, Joanna
dc.contributor.authorWojciechowska, Monika
dc.contributor.authorMiszkiewicz, Joanna
dc.contributor.authorBurmistrz, Michał
dc.contributor.authorChyży, Piotr
dc.contributor.authorMacyszyn, Julia
dc.contributor.authorLobka, Małgorzata
dc.date.accessioned2024-01-26T08:21:26Z
dc.date.available2024-01-26T08:21:26Z
dc.date.issued2023
dc.description.financePublikacja bezkosztowa
dc.description.number1
dc.description.volume13
dc.identifier.doi10.1038/S41598-023-38745-Y
dc.identifier.issn2045-2322
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/120887
dc.identifier.weblinkhttps://www.nature.com/articles/s41598-023-38745-y.pdf
dc.languageeng
dc.relation.ispartofScientific Reports
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleStructural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K
dc.typeJournalArticle
dspace.entity.typePublication