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Antibacterial Metallacarborane-Peptide Hybrids Target the Membrane Potential in a Nonlytic Mode and Are Resistant to Proteolysis
K. Fink, B. Szermer-Olearnik, A. Kędziora, B. Dudek, G. Bugla-Płoskońska, W. Goldeman, M. Gos, M. Cuprych-Belter, M. Psurski, P. Migdał, M. Uchman, TM. Goszczyński
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
- MeSH
- antibakteriální látky * farmakologie chemie chemická syntéza MeSH
- hemolýza účinky léků MeSH
- lidé MeSH
- membránové potenciály * účinky léků MeSH
- mikrobiální testy citlivosti MeSH
- proteolýza MeSH
- reaktivní formy kyslíku metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The rise of antibiotic resistance necessitates the development of innovative antimicrobial strategies. Antimicrobial peptides (AMPs), with their broad-spectrum activity and membrane-targeting mechanisms, offer an attractive alternative to conventional antibiotics but are limited by toxicity, proteolytic instability, and production costs. In this study, we report a series of novel AMP mimics combining cationic di- and tripeptides with cobalt bis(dicarbollide) (COSAN) and its iodinated analogue (I-COSAN). These metallacarborane-peptide hybrids retained the amphiphilic structure of AMPs and demonstrated potent, broad-spectrum antibacterial activity while exhibiting low hemolytic activity and cytotoxicity. Mechanistically, the best-performing conjugate induced bacterial membrane depolarization without cell lysis, accompanied by ATP depletion, reactive oxygen species overproduction, and morphological changes. Importantly, the conjugates resisted proteolytic degradation, demonstrating that a modification with a metallacarborane combines biological activity with enhanced stability. These findings introduce metallacarborane-peptide hybrids as a versatile platform for developing next-generation antimicrobials that combine the multifunctionality of AMPs with improved stability.
Citace poskytuje Crossref.org
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- $a Fink, Krzysztof $u Laboratory of Biomedical Chemistry, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław 53-114, Poland $u Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Hlavova 2030, Prague 2 128 40, Czechia $1 https://orcid.org/0000000212389653
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