Antibacterial Metallacarborane-Peptide Hybrids Target the Membrane Potential in a Nonlytic Mode and Are Resistant to Proteolysis

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Antibacterial Metallacarborane-Peptide Hybrids Target the Membrane Potential in a Nonlytic Mode and Are Resistant to Proteolysis

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Antibacterial Metallacarborane-Peptide Hybrids Target the Membrane Potential in a Nonlytic Mode and Are Resistant to Proteolysis

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

1520-4804

Svazek periodika

68

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

16076-16092

Kód UT WoS článku

001530807300001

EID výsledku v databázi Scopus

2-s2.0-105013541049