Peptide conjugates of lactoferricin analogues and antimicrobials - design, chemical synthesis, and evaluation of antimicrobial activity and mammalian cytotoxicity
Natalia Ptaszyńska , Katarzyna Olkiewicz , Joanna Okońska , Katarzyna Gucwa , Anna Łęgowska , Agata Gitlin-Domagalska , Dawid Dębowski , Jan Lica , Jan Heldt , Sławomir Milewski , Tzi Bun Ng , Krzysztof Rolka
AbstractEight new peptide conjugates composed of modified bovine lactoferricin truncated analogues (LFcinB) and one of the three antimicrobials — ciprofloxacin (CIP), levofloxacin (LVX), and fluconazole (FLC) — were synthesized. Four different linkers were applied to connect a peptide and an antimicrobial agent. The FLC-containing peptidic conjugates were synthesized using the “click chemistry” method. This novel approach is reported here for the first time. Unlike their components, CIP- and LVX-based conjugates exerted activity against Candida yeast. Similarly to the constituent peptides, synthesized conjugates showed activity against Gram-positive bacteria, especially S. epidermidis. The most active were the conjugates containing CIP linked to the peptide by the redox-sensitive disulfide bridge. Our results show a significant role of a linker between antimicrobial agent and a peptide. This was also confirmed by the lack of synergistic effects on the antimicrobial activity of the constituent compounds. Moreover, cytotoxicity assays revealed that the proposed conjugates cause a comparatively low cytotoxic effect in reference to antibiotics widely used in therapies. Therefore, they can be deliberated as attractive leading structures for the development of drugs.
|Journal series||Peptides, ISSN 0196-9781, (A 25 pkt)|
|Publication size in sheets||0.6|
|Keywords in English||Peptide conjugates, antimicrobial peptides, click chemistry, disulfide bridge, lactoferricin|
|ASJC Classification||; ; ;|
|Score||= 25.0, 24-07-2019, ArticleFromJournal|
|Publication indicators||= 0; : 2016 = 0.857; : 2017 = 2.851 (2) - 2017=2.761 (5)|
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