Novel Aeruginosin-865 from Nostoc sp. as a potent anti-inflammatory agent

Chembiochem. 2013 Nov 25;14(17):2329-37. doi: 10.1002/cbic.201300246. Epub 2013 Oct 2.

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.

Keywords: NMR spectroscopy; anti-inflammatory; cyanobacteria; drug discovery; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Glycopeptides / chemistry
  • Glycopeptides / isolation & purification
  • Glycopeptides / pharmacology*
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Lipopeptides / chemistry
  • Lipopeptides / isolation & purification
  • Lipopeptides / pharmacology*
  • Molecular Structure
  • NF-kappa B / metabolism
  • Nostoc / chemistry*
  • Nostoc / growth & development
  • Protein Transport / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Glycopeptides
  • Interleukin-8
  • Lipopeptides
  • NF-kappa B
  • aeruginosin-865
  • Intercellular Adhesion Molecule-1