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


Eight 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.
Author Natalia Ptaszyńska (FCh / DMB / LBCh)
Natalia Ptaszyńska,,
- Laboratory of Bioorganic Chemistry
, Katarzyna Olkiewicz (FCh / DMB / LBCh)
Katarzyna Olkiewicz ,,
- Laboratory of Bioorganic Chemistry
, Joanna Okońska (FCh / DMB / LBCh)
Joanna Okońska,,
- Laboratory of Bioorganic Chemistry
, Katarzyna Gucwa (FCh / DMB) - [Politechnika Gdańska]
Katarzyna Gucwa,,
- Department of Molecular Biochemistry
- Politechnika Gdańska
, Anna Łęgowska (FCh / DMB / LBCh)
Anna Łęgowska,,
- Laboratory of Bioorganic Chemistry
, Agata Gitlin-Domagalska (FCh / DMB / LBCh)
Agata Gitlin-Domagalska,,
- Laboratory of Bioorganic Chemistry
, Dawid Dębowski (FCh / DMB / LBCh)
Dawid Dębowski,,
- Laboratory of Bioorganic Chemistry
, Jan Lica
Jan Lica,,
, Jan Heldt
Jan Heldt,,
, Sławomir Milewski
Sławomir Milewski,,
et al.`
Journal seriesPeptides, ISSN 0196-9781, (A 25 pkt)
Issue year2019
Publication size in sheets0.6
Article number170079
Keywords in EnglishPeptide conjugates, antimicrobial peptides, click chemistry, disulfide bridge, lactoferricin
ASJC Classification2804 Cellular and Molecular Neuroscience; 1310 Endocrinology; 1314 Physiology; 1303 Biochemistry
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 24-07-2019, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.857; WoS Impact Factor: 2017 = 2.851 (2) - 2017=2.761 (5)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.