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Antibiotic-Based Conjugates Containing Antimicrobial HLopt2 Peptide: Design, Synthesis, Antimicrobial and Cytotoxic Activities
Abstrakt
Recent studies have shown that modified human lactoferrin 20−31 fragment, named HLopt2, possesses antibacterial and antifungal activity. Thus, we decided to synthesize and evaluate the biological activity of a series of conjugates based on this peptide and one of the antimicrobials with proven antibacterial (ciprofloxacin, CIP, and levofloxacin, LVX) or antifungal (fluconazole, FLC) activity. The drugs were covalently connected to the peptide via amide, methylenecarbonyl moieties, or a disulfide bridge. The antibacterial and antifungal activities were evaluated under Clinical and Laboratory Standard Institute (CLSI) recommended conditions or in a low-salt brain−heart infusion diluted medium (BHI1/100). Results showed that conjugation of the peptide with the drug increased its antimicrobial activity up to 4-fold. Under CLSI-recommended conditions, all the compounds revealed rather low efficiency. Among conjugates, the highest antibacterial activity was recorded for the CIP-Cys-S-S-HLopt2-NH2 (III). In BHI1/100, which had lower differentiating properties, all of the conjugates revealed low MIC and MMC (minimum inhibitory and microbicidal concentrations) values. The disulfide bridge used as a linker in the most active conjugate (III) upon incubation with S. aureus cells is reduced, releasing constituent peptide and CIP-Cys. In addition, we showed that its fluorescently labeled analogue and constituent peptide are able to be internalized into both C. albicans and S. aureus cells. Moreover, the invaluable advantage of the presented conjugates was their low toxicity to mammalian cells and very low hemolytic activity. The current research can form a solid basis for further in vivo studies and drug development.
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Autorzy (10)
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Natalia Ptaszyńska
- Wydział Chemii UG Biochemii Molekularnej
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Katarzyna Gucwa Dr inż.
- Wydział Chemii UG Biochemii Molekularnej
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Katarzyna Olkiewicz
- Wydział Chemii UG Biochemii Molekularnej
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Anna Łȩgowska
- Wydział Chemii UG Biochemii Molekularnej
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Joanna Okońska
- Wydział Chemii UG Biochemii Moleklarnej
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Agata Gitlin-Domagalska
- Wydział Chemii UG Biochemii Molekularnej
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Dawid Dȩbowski
- Wydział Chemii UG Biochemii Molekularnej
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Krzysztof Rolka
- Wydział Chemii UG Biochemii Molekularnej
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Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuły w czasopismach
- Opublikowano w:
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ACS Chemical Biology
strony 2233 - 2242,
ISSN: 1554-8929 - Język:
- angielski
- Rok wydania:
- 2019
- Opis bibliograficzny:
- Ptaszyńska N., Gucwa K., Olkiewicz K., Łȩgowska A., Okońska J., Ruczyński J., Gitlin-Domagalska A., Dȩbowski D., Milewski S., Rolka K.: Antibiotic-Based Conjugates Containing Antimicrobial HLopt2 Peptide: Design, Synthesis, Antimicrobial and Cytotoxic Activities// ACS Chemical Biology -, (2019), s.2233-2242
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1021/acschembio.9b00538
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 156 razy
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