Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity

Tanil Kocagoz; Betul Zehra Temur; Nihan Unubol; Merve Acikel Elmas; Zeynep Kanlidere; Sumeyye Cilingir; Dilan Acar; Gizem Boskan; Sumeyye Akcelik Deveci; Esma Aybakan; Aslihan Ozcan Yoner; Neval Yurttutan Uyar; Mustafa Serteser; Seray Sahsuvar; Yigit Erdemgil; Zeynep Zulfiye Yildirim Keles; Deniz Demirhan; Sandra Sakalauskaite; Rimantas Daugelavicius; Tugba Arzu Ozal Ildeniz; Ahmet Emin Atik; Erkan Mozioglu; Tarik Eren; Serap Arbak; Guldal Suyen; Ozge Can

doi:10.3390/life15020242

Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity

Tanil Kocagoz^*, Betul Zehra Temur, Nihan Unubol, Merve Acikel Elmas, Zeynep Kanlidere, Sumeyye Cilingir, Dilan Acar, Gizem Boskan, Sumeyye Akcelik Deveci, Esma Aybakan, Aslihan Ozcan Yoner, Neval Yurttutan Uyar, Mustafa Serteser, Seray Sahsuvar, Yigit Erdemgil, Zeynep Zulfiye Yildirim Keles, Deniz Demirhan, Sandra Sakalauskaite, Rimantas Daugelavicius, Tugba Arzu Ozal IldenizAhmet Emin Atik, Erkan Mozioglu, Tarik Eren, Serap Arbak, Guldal Suyen, Ozge Can^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Antimicrobial peptides (AMPs) are a diverse group of small, naturally occurring molecules that orchestrate the innate immune response of various organisms, from microorganisms to humans. Characterized by their broad-spectrum activity against bacteria, fungi and viruses, AMPs are increasingly recognized for their potential as novel therapeutic agents in the face of rising antibiotic resistance. Here, we present several newly designed AMPs, one of which, DTN6, exerts significant activity against several organisms with MIC values as low as 0.5 µg/mL. The D-TN6 peptide influences both bacteria and yeasts. Scanning electron microscopy and transmission electron microscopy results showed that the bacterial membrane is affected by D-TN6, which is resistant to proteases and is effective against antibiotic-resistant pathogens with hemolytic activity and low toxicity. The D-TN6 peptide is effective in vivo against standard S. aureus strains in wounds. Thus, D-TN6 is a potent antibiotic candidate with a broad spectrum of activity. Overall, AMPs are a promising tool for the development of next-generation antimicrobial agents that could mitigate global health threats posed by multidrug-resistant pathogens.

Original language	English
Article number	242
Journal	Life
Volume	15
Issue number	2
DOIs	https://doi.org/10.3390/life15020242
Publication status	Published - Feb 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2025 by the authors.

Keywords

antimicrobial peptides
multidrug resistance
peptide antibiotics
peptide synthesis
protease resistance
protein-mimicking peptides

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10.3390/life15020242

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Kocagoz, T., Temur, B. Z., Unubol, N., Acikel Elmas, M., Kanlidere, Z., Cilingir, S., Acar, D., Boskan, G., Akcelik Deveci, S., Aybakan, E., Ozcan Yoner, A., Yurttutan Uyar, N., Serteser, M., Sahsuvar, S., Erdemgil, Y., Yildirim Keles, Z. Z., Demirhan, D., Sakalauskaite, S., Daugelavicius, R., ... Can, O. (2025). Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity. Life, 15(2), Article 242. https://doi.org/10.3390/life15020242

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title = "Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity",

abstract = "Antimicrobial peptides (AMPs) are a diverse group of small, naturally occurring molecules that orchestrate the innate immune response of various organisms, from microorganisms to humans. Characterized by their broad-spectrum activity against bacteria, fungi and viruses, AMPs are increasingly recognized for their potential as novel therapeutic agents in the face of rising antibiotic resistance. Here, we present several newly designed AMPs, one of which, DTN6, exerts significant activity against several organisms with MIC values as low as 0.5 µg/mL. The D-TN6 peptide influences both bacteria and yeasts. Scanning electron microscopy and transmission electron microscopy results showed that the bacterial membrane is affected by D-TN6, which is resistant to proteases and is effective against antibiotic-resistant pathogens with hemolytic activity and low toxicity. The D-TN6 peptide is effective in vivo against standard S. aureus strains in wounds. Thus, D-TN6 is a potent antibiotic candidate with a broad spectrum of activity. Overall, AMPs are a promising tool for the development of next-generation antimicrobial agents that could mitigate global health threats posed by multidrug-resistant pathogens.",

keywords = "antimicrobial peptides, multidrug resistance, peptide antibiotics, peptide synthesis, protease resistance, protein-mimicking peptides",

author = "Tanil Kocagoz and Temur, \{Betul Zehra\} and Nihan Unubol and \{Acikel Elmas\}, Merve and Zeynep Kanlidere and Sumeyye Cilingir and Dilan Acar and Gizem Boskan and \{Akcelik Deveci\}, Sumeyye and Esma Aybakan and \{Ozcan Yoner\}, Aslihan and \{Yurttutan Uyar\}, Neval and Mustafa Serteser and Seray Sahsuvar and Yigit Erdemgil and \{Yildirim Keles\}, \{Zeynep Zulfiye\} and Deniz Demirhan and Sandra Sakalauskaite and Rimantas Daugelavicius and \{Ozal Ildeniz\}, \{Tugba Arzu\} and Atik, \{Ahmet Emin\} and Erkan Mozioglu and Tarik Eren and Serap Arbak and Guldal Suyen and Ozge Can",

note = "Publisher Copyright: {\textcopyright} 2025 by the authors.",

year = "2025",

month = feb,

doi = "10.3390/life15020242",

language = "English",

volume = "15",

journal = "Life",

issn = "2075-1729",

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Kocagoz, T, Temur, BZ, Unubol, N, Acikel Elmas, M, Kanlidere, Z, Cilingir, S, Acar, D, Boskan, G, Akcelik Deveci, S, Aybakan, E, Ozcan Yoner, A, Yurttutan Uyar, N, Serteser, M, Sahsuvar, S, Erdemgil, Y, Yildirim Keles, ZZ, Demirhan, D, Sakalauskaite, S, Daugelavicius, R, Ozal Ildeniz, TA, Atik, AE, Mozioglu, E, Eren, T, Arbak, S, Suyen, G & Can, O 2025, 'Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity', Life, vol. 15, no. 2, 242. https://doi.org/10.3390/life15020242

TY - JOUR

T1 - Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity

AU - Kocagoz, Tanil

AU - Temur, Betul Zehra

AU - Unubol, Nihan

AU - Acikel Elmas, Merve

AU - Kanlidere, Zeynep

AU - Cilingir, Sumeyye

AU - Acar, Dilan

AU - Boskan, Gizem

AU - Akcelik Deveci, Sumeyye

AU - Aybakan, Esma

AU - Ozcan Yoner, Aslihan

AU - Yurttutan Uyar, Neval

AU - Serteser, Mustafa

AU - Sahsuvar, Seray

AU - Erdemgil, Yigit

AU - Yildirim Keles, Zeynep Zulfiye

AU - Demirhan, Deniz

AU - Sakalauskaite, Sandra

AU - Daugelavicius, Rimantas

AU - Ozal Ildeniz, Tugba Arzu

AU - Atik, Ahmet Emin

AU - Mozioglu, Erkan

AU - Eren, Tarik

AU - Arbak, Serap

AU - Suyen, Guldal

AU - Can, Ozge

PY - 2025/2

Y1 - 2025/2

N2 - Antimicrobial peptides (AMPs) are a diverse group of small, naturally occurring molecules that orchestrate the innate immune response of various organisms, from microorganisms to humans. Characterized by their broad-spectrum activity against bacteria, fungi and viruses, AMPs are increasingly recognized for their potential as novel therapeutic agents in the face of rising antibiotic resistance. Here, we present several newly designed AMPs, one of which, DTN6, exerts significant activity against several organisms with MIC values as low as 0.5 µg/mL. The D-TN6 peptide influences both bacteria and yeasts. Scanning electron microscopy and transmission electron microscopy results showed that the bacterial membrane is affected by D-TN6, which is resistant to proteases and is effective against antibiotic-resistant pathogens with hemolytic activity and low toxicity. The D-TN6 peptide is effective in vivo against standard S. aureus strains in wounds. Thus, D-TN6 is a potent antibiotic candidate with a broad spectrum of activity. Overall, AMPs are a promising tool for the development of next-generation antimicrobial agents that could mitigate global health threats posed by multidrug-resistant pathogens.

AB - Antimicrobial peptides (AMPs) are a diverse group of small, naturally occurring molecules that orchestrate the innate immune response of various organisms, from microorganisms to humans. Characterized by their broad-spectrum activity against bacteria, fungi and viruses, AMPs are increasingly recognized for their potential as novel therapeutic agents in the face of rising antibiotic resistance. Here, we present several newly designed AMPs, one of which, DTN6, exerts significant activity against several organisms with MIC values as low as 0.5 µg/mL. The D-TN6 peptide influences both bacteria and yeasts. Scanning electron microscopy and transmission electron microscopy results showed that the bacterial membrane is affected by D-TN6, which is resistant to proteases and is effective against antibiotic-resistant pathogens with hemolytic activity and low toxicity. The D-TN6 peptide is effective in vivo against standard S. aureus strains in wounds. Thus, D-TN6 is a potent antibiotic candidate with a broad spectrum of activity. Overall, AMPs are a promising tool for the development of next-generation antimicrobial agents that could mitigate global health threats posed by multidrug-resistant pathogens.

KW - antimicrobial peptides

KW - multidrug resistance

KW - peptide antibiotics

KW - peptide synthesis

KW - protease resistance

KW - protein-mimicking peptides

UR - https://www.scopus.com/pages/publications/85219041979

U2 - 10.3390/life15020242

DO - 10.3390/life15020242

M3 - Article

AN - SCOPUS:85219041979

SN - 2075-1729

VL - 15

JO - Life

JF - Life

IS - 2

M1 - 242

ER -

Protease-Resistant, Broad-Spectrum Antimicrobial Peptides with High Antibacterial and Antifungal Activity

Abstract

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Keywords

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