Formation, characterization, and toxicity of the glutathione and cysteine conjugates of toxic heptapeptide microcystins

Chem Res Toxicol. 1992 Sep-Oct;5(5):591-6. doi: 10.1021/tx00029a002.

Abstract

Microcystins LR, YR, and RR, cyclic heptapeptide hepatotoxins produced by cyanobacteria, were synthetically converted into glutathione (GSH) and cysteine (Cys) conjugates. Fast atom bombardment mass spectra showed [M + H]+ ions corresponding to GSH and Cys conjugates of microcystins LR, YR, and RR for the obtained compounds. 1H NMR spectral analyses revealed that two singlet signals of olefinic protons of N-methyldehydroalanine (Mdha) in microcystins disappeared in the conjugates, confirming that thiols of GSH and Cys added nucleophilically to the alpha, beta-unsaturated carbonyl of the Mdha moiety. On examination of the 50% lethal dose (LD50) with intravenous injection using mice, both GSH and Cys conjugates showed reduction in toxicity compared with microcystins, but their toxicity still remained. Microcystin LR and its GSH conjugate were separated and identified in a standard mixture by using a frit-fast atom bombardment liquid chromatography/mass spectrometry (Frit-FAB LC/MS) method. Obtained conjugates in the present study would be important compounds as the standard samples for study of metabolism of microcystins, and the Frit-FAB LC/MS method would be applicable to mass spectrometric identification of metabolites of microcystins.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Cyanobacteria / chemistry
  • Cysteine / chemistry
  • Gas Chromatography-Mass Spectrometry
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Lethal Dose 50
  • Liver / drug effects
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Marine Toxins
  • Mice
  • Microcystins
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / toxicity*
  • Spectrometry, Mass, Fast Atom Bombardment

Substances

  • Marine Toxins
  • Microcystins
  • Peptides, Cyclic
  • microcystin YR
  • microcystin RR
  • cyanoginosin LR
  • Glutathione
  • Cysteine