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
AbstractAn 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.
|Journal series||International Journal of Molecular Sciences, ISSN 1422-0067, (N/A 140 pkt)|
|Publication size in sheets||1.05|
|Keywords in English||ESKAPE pathogens, Staphylococcus aureus, KR12, LL-37, lipopeptide, critical aggregation concentration, CD spectroscopy, NMR, biofilm, cytotoxicity|
|ASJC Classification||; ; ; ; ; ; ;|
|License||Journal (articles only); published final; ; with publication|
|Score||= 140.0, 02-05-2020, ArticleFromJournal|
|Publication indicators||= 0.000; : 2018 = 1.224; : 2018 = 4.183 (2) - 2018=4.331 (5)|
|Citation count*||2 (2020-07-08)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.