Lipidated Analogs of the LL-37-Derived Peptide Fragment KR12—Structural Analysis, Surface-Active Properties and Antimicrobial Activity

International Journal of Molecular Sciences

Wioletta Barańska-Rybak¹  Wojciech Kamysz²  Maciej Jaśkiewicz²  Damian Neubauer²  Sylwia Bartoszewska²  Marta Bauer²  Elżbieta Kamysz³  Emilia Sikorska⁴ 

[1] Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gdańsk, 80-214 Gdańsk, Poland;Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland;Laboratory of Chemistry of Biological Macromolecules, Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdańsk, 80-308 Gdańsk, Poland;Laboratory of Structural Studies of Biopolymers, Department of Organic Chemistry, Faculty of Chemistry, University of Gdańsk, 80-308 Gdańsk, Poland;

关键词: eskape pathogens;    staphylococcus aureus;    kr12;    ll-37;    lipopeptide;    critical aggregation concentration;    cd spectroscopy;    nmr;    biofilm;    cytotoxicity;   

DOI  :  10.3390/ijms21030887

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown