Antibacterial Metallacarborane-Peptide Hybrids Target the Membrane Potential in a Nonlytic Mode and Are Resistant to Proteolysis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F25%3A10501671" target="_blank" >RIV/00216208:11310/25:10501671 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=_T3SQCMAG4" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=_T3SQCMAG4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.5c01025" target="_blank" >10.1021/acs.jmedchem.5c01025</a>
Alternative languages
Result language
angličtina
Original language name
Antibacterial Metallacarborane-Peptide Hybrids Target the Membrane Potential in a Nonlytic Mode and Are Resistant to Proteolysis
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
1520-4804
Volume of the periodical
68
Issue of the periodical within the volume
15
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
16076-16092
UT code for WoS article
001530807300001
EID of the result in the Scopus database
2-s2.0-105013541049