Triazole-Bridged Peptides with Enhanced Antimicrobial Activity and Potency against Pathogenic Bacteria
Open accessAbstract
There are still no linear antimicrobial peptides (AMPs) available as a treatment option against bacterial infections. This is caused by several drawbacks that come with AMPs such as limited proteolytic stability and low selectivity against human cells. In this work, we screened a small library of rationally designed new peptides based on the cell-penetrating peptide sC18* toward their antimicrobial activity. We identified several effective novel AMPs and chose one out of this group to further increase its potency. Therefore, we introduced a triazole bridge at different positions to provide a preformed helical structure, assuming that this modification would improve (i) proteolytic stability and (ii) membrane activity. Indeed, placing the triazole bridge within the hydrophilic part of the linear analogue highly increased membrane activity as well as stability against enzymatic digestion. The new peptides, 8A and 8B, demonstrated high activity against several bacterial species tested including pathogenic N. gonorrhoeae and methicillin-resistant S. aureus . Since they exhibited significantly good tolerability against human fibroblast and blood cells, these novel peptides offer true alternatives for future clinical applications and are worth studying in more detail.
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Cites
Tornøe, C. W., Christensen, C., & Meldal, M. (2002) · The Journal of Organic Chemistry · doi:10.1021/jo011148j · Cited by 8,696 · see citing works
Methods for in vitro evaluating antimicrobial activity: A review
Balouiri, M., Sadiki, M., & Ibnsouda, S. K. (2016) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2015.11.005 · Cited by 7,264 · see citing works
Antimicrobial host defence peptides: functions and clinical potential
Mookherjee, N., Anderson, M. A., Haagsman, H. P., & Davidson, D. J. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0058-8 · Cited by 1,502 · see citing works
Molecular mechanisms of antibiotic resistance revisited
Darby, E. M., Trampari, E., Siasat, P., Gaya, M. S., Alav, I., Webber, M. A., & Blair, J. M. A. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00820-y · Cited by 1,398 · see citing works
HELIQUEST: a web server to screen sequences with specific α-helical properties
Gautier, R., Douguet, D., Antonny, B., & Drin, G. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn392 · Cited by 1,236 · see citing works
Recognition of transmembrane helices by the endoplasmic reticulum translocon
Hessa, T., Kim, H., Bihlmaier, K., Lundin, C., Boekel, J., Andersson, H. M., Nilsson, I., White, S. H., & von HEIJNE, G. (2005) · Nature · doi:10.1038/nature03216 · Cited by 996 · see citing works
From antimicrobial to anticancer peptides. A review
Gaspar, D., Veiga, A. S., & Castanho, M. A. R. B. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00294 · Cited by 762 · see citing works
Cell penetrating peptides: A concise review with emphasis on biomedical applications
Derakhshankhah, H., & Jafari, S. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.09.097 · Cited by 380 · see citing works
Mode-of-Action of Antimicrobial Peptides: Membrane Disruption vs. Intracellular Mechanisms
Benfield, A. H., & Henriques, S. T. (2020) · Frontiers in Medical Technology · doi:10.3389/fmedt.2020.610997 · Cited by 372 · see citing works
Manning, M. C., & Woody, R. W. (1991) · Biopolymers · doi:10.1002/bip.360310511 · Cited by 328 · see citing works
Mechanistic Landscape of Membrane-Permeabilizing Peptides
Guha, S., Ghimire, J., Wu, E., & Wimley, W. C. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00520 · Cited by 283 · see citing works
Nakamura, L. K., Roberts, M. S., & Cohan, F. M. (1999) · INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY · doi:10.1099/00207713-49-3-1211 · Cited by 186 · see citing works
Scrima, M., Isaad, A. L. C., Rovero, P., Papini, A. M., Chorev, M., & Papini, A. M. (2009) · European Journal of Organic Chemistry · doi:10.1002/ejoc.200901157 · Cited by 117 · see citing works
Self-citationRole and modulation of the secondary structure of antimicrobial peptides to improve selectivity
Liang, Y., Zhang, X., Yuan, Y., Bao, Y., & Xiong, M. (2020) · Biomaterials Science · doi:10.1039/d0bm00801j · Cited by 103 · see citing works
Protease-Resistant Peptides for Targeting and Intracellular Delivery of Therapeutics
Lucana, M. C., Arruga, Y., Petrachi, E., Roig, A., Lucchi, R., & Oller-Salvia, B. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13122065 · Cited by 102 · see citing works
Dunlap, C. A., Bowman, M. J., & Zeigler, D. R. (2019) · Antonie van Leeuwenhoek · doi:10.1007/s10482-019-01354-9 · Cited by 83 · see citing works
Omardien, S., Drijfhout, J. W., Vaz, F. M., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2018.06.004 · Cited by 82 · see citing works
Štumpf, S., Hostnik, G., Primožič, M., Leitgeb, M., Salminen, J., & Bren, U. (2020) · Molecules · doi:10.3390/molecules25122947 · Cited by 65 · see citing works
Feni, L., Parente, S., Robert, C., Gazzola, S., Arosio, D., Piarulli, U., & Neundorf, I. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00292 · Cited by 62 · see citing works
Self-citationNeundorf, I. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-3588-4_7 · Cited by 61 · see citing works
Self-citationCurrent developments in antibiotic discovery
Hegemann, J. D., Birkelbach, J., Walesch, S., & Müller, R. (2022) · EMBO Reports · doi:10.15252/embr.202256184 · Cited by 59 · see citing works
Antibiofilm properties of cathelicidin LL-37: an in-depth review
Memariani, H., & Memariani, M. (2023) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-023-03545-z · Cited by 59 · see citing works
Horn, M., Reichart, F., Natividad-Tietz, S., et al. (2015) · Chemical Communications · doi:10.1039/c5cc08938g · Cited by 57 · see citing works
Unnatural amino acids: promising implications for the development of new antimicrobial peptides
Wang, X., Yang, X., Wang, Q., & Meng, D. (2022) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2022.2047008 · Cited by 55 · see citing works
Yao, L., Liu, Q., Lei, Z., & Sun, T. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.126819 · Cited by 40 · see citing works
Short Peptides and Their Mimetics as Potent Antibacterial Agents and Antibiotic Adjuvants
Panjla, A., Kaul, G., Chopra, S., Titz, A., & Verma, S. K. (2021) · ACS Chemical Biology · doi:10.1021/acschembio.1c00626 · Cited by 36 · see citing works
Conformational Dynamics of Asparagine at Coiled-Coil Interfaces
Thomas, F., Niitsu, A., Oregioni, A., Bartlett, G. J., & Woolfson, D. N. (2017) · Biochemistry · doi:10.1021/acs.biochem.7b00848 · Cited by 33 · see citing works
Reichart, F., Horn, M., & Neundorf, I. (2016) · Journal of Peptide Science · doi:10.1002/psc.2885 · Cited by 26 · see citing works
Self-citationAntimicrobial peptides for novel antiviral strategies in the current post‐COVID‐19 pandemic
Loffredo, M. R., Nencioni, L., Mangoni, M. L., & Casciaro, B. (2023) · Journal of Peptide Science · doi:10.1002/psc.3534 · Cited by 25 · see citing works
Cronenberg, T., Hennes, M., Wielert, I., & Maier, B. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009251 · Cited by 24 · see citing works
Self-citationMultistep optimization of a cell-penetrating peptide towards its antimicrobial activity
Drexelius, M. G., Reinhardt, A., Grabeck, J., et al. (2020) · Biochemical Journal · doi:10.1042/bcj20200698 · Cited by 22 · see citing works
Self-citationSynthesis, Characterization, and Antimicrobial Activity of Ultra-Short Cationic β-Peptides
Chowdhary, R., Mubarak, M. M., Kantroo, H. A., et al. (2023) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.3c00238 · Cited by 21 · see citing works
Evaluating the effects of hydrophobic and cationic residues on antimicrobial peptide self-assembly
Cao, F., Ma, G., Song, M., Zhu, G., Mei, L., & Qin, Q. (2021) · Soft Matter · doi:10.1039/d1sm00096a · Cited by 17 · see citing works
D’Ercole, A., Sabatino, G., Pacini, L., et al. (2020) · Peptide Science · doi:10.1002/pep2.24159 · Cited by 15 · see citing works
Has, C., & Das, S. L. (2023) · The Journal of Membrane Biology · doi:10.1007/s00232-023-00289-7 · Cited by 13 · see citing works
Shaikh, A. Y., Björkling, F., Żabicka, D., Tomczak, M., Urbaś, M., Domračeva, I., Kreicberga, A., & Franzyk, H. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106876 · Cited by 11 · see citing works
Topoisomeric Membrane-Active Peptides: A Review of the Last Two Decades
Carrera-Aubesart, A., Gallo, M., Defaus, S., Todorovski, T., & Andreu, D. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15102451 · Cited by 11 · see citing works
Comparing Variants of the Cell-Penetrating Peptide sC18 to Design Peptide-Drug Conjugates
Grabeck, J., Lützenburg, T., Frommelt, P., et al. (2022) · Molecules · doi:10.3390/molecules27196656 · Cited by 9 · see citing works
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Research works printed but not linked: 1
- Antonie van Leeuwenhoek, Int. J. Gen. Mol. Microbiol. 2020, 113 (1), 1- 12.
Cited by
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Varró, N., Mándityné Huszka, B., Erdei, E., Mándoki, A., & Mándity, I. M. (2025) · Chemistry–Methods · doi:10.1002/cmtd.202500010 · Cited by 8 · see citing works
- Authors
- Grabeck, J., Mayer, J., Miltz, A., Casoria, M., Quagliata, M., Meinberger, D., Klatt, A. R., Wielert, I., Maier, B., Papini, A. M., & Neundorf, I.
- Affiliations
- University of Cologne (DE)
- University of Florence (IT)
- Corresponding author
- Neundorf, Ines
- ORCID
- Venue
- ACS Infectious Diseases
- Publisher
- American Chemical Society (ACS)
- Published
- 2024-06-17
- Volume
- 10
- Issue
- 8
- Pages
- 2717-2727
- ISSN
- 2373-8227 (ISSN-L)
- OpenAlex
- W4399723120
- Cited by
- 7
- References
- 38
- Citations by year
- 2026: 1 · 2025: 6
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- green
- pubs.acs.org
- Licence
- Locations
- ACS Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (NE14-10)
- EUniWell
- Erasmus+ exchange program
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- antimicrobial peptides, peptide library screening, proteolytic stability, membrane activity, Neisseria gonorrhoeae, methicillin-resistant Staphylococcus aureus, antibacterial activity, rational peptide design
- MeSH terms
- Antimicrobial Peptides, Anti-Bacterial Agents, Bacteria, Fibroblasts, Humans, Microbial Sensitivity Tests, Neisseria gonorrhoeae, Triazoles, Methicillin-Resistant Staphylococcus aureus
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