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

• Published in: Chembiochem : a European journal of chemical biology Vol. 14; no. 17; pp. 2329 - 2337
• Main Authors: Kapuścik, Aleksandra, Hrouzek, Pavel, Kuzma, Marek, Bártová, Simona, Novák, Petr, Jokela, Jouni, Pflüger, Maren, Eger, Andreas, Hundsberger, Harald, Kopecký, Jiří
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 25.11.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Active Transport, Cell Nucleus - drug effects; anti-inflammatory; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biochemistry & Molecular Biology; Cell Line; Chemistry, Medicinal; cyanobacteria; Dose-Response Relationship, Drug; Down-Regulation - drug effects; drug discovery; Glycopeptides - chemistry; Glycopeptides - isolation & purification; Glycopeptides - pharmacology; Humans; Intercellular Adhesion Molecule-1 - biosynthesis; Interleukin-8 - biosynthesis; Life Sciences & Biomedicine; Lipopeptides - chemistry; Lipopeptides - isolation & purification; Lipopeptides - pharmacology; Liquid chromatography; Mass spectrometry; Molecular Structure; NF-kappa B - metabolism; NMR spectroscopy; Nostoc - chemistry; Nostoc - growth & development; peptides; Pharmacology & Pharmacy; Protein Transport - drug effects; Science & Technology; Structure-Activity Relationship; Translocation; MAP KINASE; C-PHYCOCYANIN; peptides; ALPHA; NODULARIA-SPUMIGENA; ADHESION; INHIBITION; drug discovery; PATHWAY; cyanobacteria; ENDOTHELIAL-CELLS; anti-inflammatory; NMR spectroscopy; NF-KAPPA-B; TRANSCRIPTIONAL REGULATION
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.201300246

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. Calm down: Anti‐inflammatory activity of the new aeruginosin Aer‐865 is reported. In TNF‐α‐stimulated endothelial cells, Aer‐865 downregulates IL‐8 and ICAM‐1 and is associated with inhibition of NF‐κB translocation to the nucleus. In this respect Aer‐865 can be considered an interesting immunomodulatory agent.