Novel Aeruginosin-865 from Nostoc sp. as a Potent Anti-inflammatory Agent

Authors

  • Aleksandra Kapuścik,

    1. Department of Phototrophic Microorganisms–ALGATECH, Institute of Microbiology, Academy of Science of the Czech Republic, Opatovický mlýn, 379 81 Třeboň (Czech Republic)
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  • Dr. Pavel Hrouzek,

    Corresponding author
    1. Department of Phototrophic Microorganisms–ALGATECH, Institute of Microbiology, Academy of Science of the Czech Republic, Opatovický mlýn, 379 81 Třeboň (Czech Republic)
    2. Institute of Chemistry, Faculty of Sciences, University of South Bohemia, Branišovská 31, 370 01 České Budĕjovice (Czech Republic)
    • Department of Phototrophic Microorganisms–ALGATECH, Institute of Microbiology, Academy of Science of the Czech Republic, Opatovický mlýn, 379 81 Třeboň (Czech Republic)

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  • Dr. Marek Kuzma,

    1. Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Science of the Czech Republic, Vídeňská 1083, 142 20 Prague (Czech Republic)
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  • Simona Bártová,

    1. Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Science of the Czech Republic, Vídeňská 1083, 142 20 Prague (Czech Republic)
    2. Department of Analytical Chemistry, Institute of Chemical Technology, Technická 5, 166 28 Prague–Dejvice (Czech Republic)
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  • Dr. Petr Novák,

    1. Laboratory of Molecular Structure Characterization, Institute of Microbiology, Academy of Science of the Czech Republic, Vídeňská 1083, 142 20 Prague (Czech Republic)
    2. Department of Biochemistry, Faculty of Sciences, Charles University, Hlavova 8, 12840 Prague (Czech Republic)
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  • Dr. Jouni Jokela,

    1. Department of Food and Environmental Sciences, Division of Microbiology, University of Helsinki, P.O. Box 56, Viikinkaari 9, 00014 Helsinki (Finland)
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  • Maren Pflüger,

    1. Department of Medical and Pharmaceutical Biotechnology, University of Applied Sciences, Piaristengasse 1, 3500 Krems (Austria)
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  • Dr. Andreas Eger,

    1. Department of Medical and Pharmaceutical Biotechnology, University of Applied Sciences, Piaristengasse 1, 3500 Krems (Austria)
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  • Dr. Harald Hundsberger,

    1. Department of Medical and Pharmaceutical Biotechnology, University of Applied Sciences, Piaristengasse 1, 3500 Krems (Austria)
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  • Dr. Jiří Kopecký

    1. Department of Phototrophic Microorganisms–ALGATECH, Institute of Microbiology, Academy of Science of the Czech Republic, Opatovický mlýn, 379 81 Třeboň (Czech Republic)
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Abstract

Aeruginosin-865 (Aer-865), isolated from terrestrial cyanobacterium Nostoc sp. Lukešová 30/93, is the first aeruginosin-type peptide containing both a fatty acid and a carbohydrate moiety, and is the first aeruginosin to be found in the genus Nostoc. Mass spectrometry, chemical and spectroscopic analysis as well as one- and two-dimensional NMR and chiral HPLC analysis of Marfey derivatives were applied to determine the peptidic sequence: D-Hpla, D-Leu, 5-OH-Choi, Agma, with hexanoic and mannopyranosyl uronic acid moieties linked to Choi. We used an AlphaLISA assay to measure the levels of proinflammatory mediators IL-8 and ICAM-1 in hTNF-α-stimulated HLMVECs. Aer-865 showed significant reduction of both: with EC50 values of (3.5±1.5) μg mL−1 ((4.0±1.7) μM) and (50.0±13.4) μg mL−1 ((57.8±15.5) μM), respectively. Confocal laser scanning microscopy revealed that the anti-inflammatory effect of Aer-865 was directly associated with inhibition of NF-κB translocation to the nucleus. Moreover, Aer-865 did not show any cytotoxic effect.

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