title: Novel Aeruginosin-865 from Nostoc sp. as a potent anti-inflammatory agent.
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.
authors.affiliation: Department of Phototrophic Microorganisms-ALGATECH, Institute of Microbiology, Academy of Science of the Czech Republic, Opatovický mlýn, 379 81 Třeboň (Czech Republic).
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kapuścik
authors.forename: Pavel
authors.initials: P
authors.lastname: Hrouzek
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzma
authors.forename: Simona
authors.initials: S
authors.lastname: Bártová
authors.forename: Petr
authors.initials: P
authors.lastname: Novák
authors.forename: Jouni
authors.initials: J
authors.lastname: Jokela
authors.forename: Maren
authors.initials: M
authors.lastname: Pflüger
authors.forename: Andreas
authors.initials: A
authors.lastname: Eger
authors.forename: Harald
authors.initials: H
authors.lastname: Hundsberger
authors.forename: Jiří
authors.initials: J
authors.lastname: Kopecký
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006020:Glycopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D055666:Lipopeptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D046937:Nostoc / Q000737:chemistry* / Q000254:growth & development; D021381:Protein Transport / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006020:Glycopeptides; D016209:Interleukin-8; D055666:Lipopeptides; D016328:NF-kappa B; C000589019:aeruginosin-865; D018799:Intercellular Adhesion Molecule-1
keywords: NMR spectroscopy; anti-inflammatory; cyanobacteria; drug discovery; peptides