Lipidated analogs of the LL-37-derived peptide fragment KR12 - structural analysis, surface-active properties and antimicrobial activity

Elżbieta Kamysz , Emilia Sikorska , Maciej Jaśkiewicz , Marta Bauer , Damian Neubauer , Sylwia Bartoszewska , Wioletta Barańska-Rybak , Wojciech Kamysz

Abstract

An increasing number of multidrug-resistant pathogens is a serious problem of modern medicine and new antibiotics are highly demanded. In this study, different n-alkyl acids (C2-C14) and aromatic acids (benzoic and trans-cinnamic) were conjugated to the N-terminus of KR12 amide. The effect of this modification on antimicrobial activity (ESKAPE bacteria and biofilm of Staphylococcus aureus) and cytotoxicity (human red blood cells and HaCaT cell line) was examined. The effect of lipophilic modifications on helicity was studied by CD spectroscopy, whereas peptide self-assembly was studied by surface tension measurements and NMR spectroscopy. As shown, conjugation of the KR12-NH2 peptide with C4-C14 fatty acid chains enhanced the antimicrobial activity with an optimum demonstrated by C8-KR12-NH2 (MIC 1–4 μg/mL against ESKAPE strains; MBEC of S. aureus 4–16 μg/mL). Correlation between antimicrobial activity and self-assembly behavior of C14-KR12-NH2 and C8-KR12-NH2 has shown that the former self-assembled into larger aggregated structures, which reduced its antimicrobial activity. In conclusion, N-terminal modification can enhance antimicrobial activity of KR12-NH2; however, at the same time, the cytotoxicity increases. It seems that the selectivity against pathogens over human cells can be achieved through conjugation of peptide N-terminus with appropriate n-alkyl fatty and aromatic acids.
Author Elżbieta Kamysz (FCh/DMBt/LChBM)
Elżbieta Kamysz,,
- Laboratory of Chemistry of Biological Macromolecules
, Emilia Sikorska (FCh/DOCh/PBSB)
Emilia Sikorska,,
- Pracownia Badań Strukturalnych Biopolimerów
, Maciej Jaśkiewicz
Maciej Jaśkiewicz,,
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, Marta Bauer
Marta Bauer,,
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, Damian Neubauer
Damian Neubauer,,
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, Sylwia Bartoszewska
Sylwia Bartoszewska,,
-
, Wioletta Barańska-Rybak
Wioletta Barańska-Rybak,,
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, Wojciech Kamysz
Wojciech Kamysz,,
-
Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)
Issue year2020
Vol21
No3
Pages1-22
Publication size in sheets1.05
Article number887
Keywords in EnglishESKAPE pathogens, Staphylococcus aureus, KR12, LL-37, lipopeptide, critical aggregation concentration, CD spectroscopy, NMR, biofilm, cytotoxicity
ASJC Classification2700 General Medicine; 1312 Molecular Biology; 1503 Catalysis; 1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1607 Spectroscopy; 1706 Computer Science Applications
DOIDOI:10.3390/ijms21030887
URL https://doi.org/10.3390/ijms21030887
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 02-05-2020, ArticleFromJournal
Publication indicators WoS Citations = 0.000; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.224; WoS Impact Factor: 2018 = 4.183 (2) - 2018=4.331 (5)
Citation count*2 (2020-07-08)
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