A novel nitroimidazole compound formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-guanosine

J Am Chem Soc. 2001 Dec 12;123(49):12147-51. doi: 10.1021/ja004296k.

Abstract

Peroxynitrite reacts with 2',3',5'-tri-O-acetyl-guanosine to yield a novel compound identified as 1-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6). This characterization was achieved using a combination of UV/vis spectroscopy and ESI-MS. Additionally, 1-(beta-D-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole (6a) was synthesized by an independent route, characterized by UV/vis spectroscopy, ESI-MS, and (1)H- and (13)C NMR, and shown to be identical to deacetylated 6. This product is extremely stable in aqueous solution at both pH extremes and is formed in significant yields. These characteristics suggest that this lesion may be useful as a specific biomarker of peroxynitrite-induced DNA damage. We also observed formation of 2',3',5'-tri-O-acetyl-8-nitroguanosine (2',3',5'-tri-O-acetyl-8-NO(2)()Guo), 2-amino-5-[(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one (2',3',5'-tri-O-acetyl-Iz), and the peroxynitrite-induced oxidation products of 2',3',5'-tri-O-acetyl-8-oxoGuo. The formation of 6 and 2',3',5'-tri-O-acetyl-8-NO(2)()Guo was rationalized by a mechanism invoking formation of the guanine radical.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers / chemistry
  • DNA Damage
  • Guanosine / analogs & derivatives*
  • Guanosine / chemistry*
  • Humans
  • Mutagens / chemistry
  • Mutagens / toxicity
  • Nitroimidazoles / chemical synthesis
  • Nitroimidazoles / chemistry*
  • Nuclear Magnetic Resonance, Biomolecular
  • Oxidation-Reduction
  • Peroxynitrous Acid / chemistry*
  • Peroxynitrous Acid / toxicity
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet

Substances

  • 1-(2,3,5-tri-O-acetyl-erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole
  • 1-(erythro-pentofuranosyl)-5-guanidino-4-nitroimidazole
  • Biomarkers
  • Mutagens
  • Nitroimidazoles
  • Guanosine
  • Peroxynitrous Acid
  • triacetylguanosine