Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K
Abstract Given 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 s...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38745-y |
| _version_ | 1797453333201420288 |
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| author | Julia Macyszyn Piotr Chyży Michał Burmistrz Małgorzata Lobka Joanna Miszkiewicz Monika Wojciechowska Joanna Trylska |
| author_facet | Julia Macyszyn Piotr Chyży Michał Burmistrz Małgorzata Lobka Joanna Miszkiewicz Monika Wojciechowska Joanna Trylska |
| author_sort | Julia Macyszyn |
| collection | DOAJ |
| description | Abstract Given 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. |
| first_indexed | 2024-03-09T15:21:18Z |
| format | Article |
| id | doaj.art-4620ee9ebd454de4b5937be53bc5b2bf |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:21:18Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4620ee9ebd454de4b5937be53bc5b2bf2023-11-26T12:47:32ZengNature PortfolioScientific Reports2045-23222023-09-0113111310.1038/s41598-023-38745-yStructural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3KJulia Macyszyn0Piotr Chyży1Michał Burmistrz2Małgorzata Lobka3Joanna Miszkiewicz4Monika Wojciechowska5Joanna Trylska6Centre of New Technologies, University of WarsawCentre of New Technologies, University of WarsawCentre of New Technologies, University of WarsawCentre of New Technologies, University of WarsawCentre of New Technologies, University of WarsawCentre of New Technologies, University of WarsawCentre of New Technologies, University of WarsawAbstract Given 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.https://doi.org/10.1038/s41598-023-38745-y |
| spellingShingle | Julia Macyszyn Piotr Chyży Michał Burmistrz Małgorzata Lobka Joanna Miszkiewicz Monika Wojciechowska Joanna Trylska Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K Scientific Reports |
| title | Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K |
| title_full | Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K |
| title_fullStr | Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K |
| title_full_unstemmed | Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K |
| title_short | Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)3K |
| title_sort | structural dynamics influences the antibacterial activity of a cell penetrating peptide kff 3k |
| url | https://doi.org/10.1038/s41598-023-38745-y |
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