Synthesis and characterization of isotopically enriched pyrimidine deoxynucleoside oxidation damage products

Christopher J. LaFrancois, June Fujimoto, Lawrence Sowers

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Oxidative damage to DNA is an established source of genomic instability. In this paper, we describe the synthesis and characterization of several pyrimidine deoxynucleoside oxidation damage products, enriched with stable isotopes. These products include the 2'-deoxynucleoside derivatives of 5- (hydroxymethyl)uracil, 5-formyluracil, 5-hydroxyuracil, 5-(hydroxymethyl)- cytosine, 5-formylcytosine, and 5-hydroxycytosine. The common precursor is 2'-deoxy-2''-deutero[1,3-15N]uridine. Additional stable isotopes are added during functional group conversions. Characterization of these derivatives includes mass spectrometry and 1H and 15N NMR spectroscopy. Proton and nitrogen NMR studies reported here allow an examination of the influence of the modification on sugar conformation and tautomeric equilibrium, properties likely to be important in understanding the biological consequences of these DNA damage products.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalChemical Research in Toxicology
Volume11
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Isotopes
DNA Damage
Derivatives
Oxidation
Uracil
Genomic Instability
Uridine
Cytosine
DNA
Sugars
Functional groups
Nuclear magnetic resonance spectroscopy
Mass spectrometry
Conformations
Protons
Mass Spectrometry
Magnetic Resonance Spectroscopy
Nitrogen
Nuclear magnetic resonance
pyrimidine

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Synthesis and characterization of isotopically enriched pyrimidine deoxynucleoside oxidation damage products. / LaFrancois, Christopher J.; Fujimoto, June; Sowers, Lawrence.

In: Chemical Research in Toxicology, Vol. 11, No. 1, 1998, p. 75-83.

Research output: Contribution to journalArticle

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