SYNTHESIS AND CHARACTERIZATION OF ISOTOPICALLY ENRICHED PYRIMIDINE DEOXYNUCLEOSIDE OXIDATION DAMAGE PRODUCTS

Oxidative damage to DNA is an established source of genomic instabilit y. In this paper, we describe the synthesis and characterization of se veral pyrimidine deoxynucleoside oxidation damage products, enriched w ith stable isotopes. These products include the 2'-deoxynucleoside der ivatives of 5-(hydroxymethyl)uracil, 5-formyluracil, 5-hydroxyuracil, 5-(hydroxymethyl)cytosine, 5-formylcytosine, and 5-hydroxycytosine. Th e common precursor is 2'-deoxy-2 ''-deutero[1,3-N-15]uridine. Addition al stable isotopes are added during functional group conversions. Char acterization of these derivatives includes mass spectrometry and H-1 a nd N-15 NMR spectroscopy. Proton and nitrogen NMR studies reported her e allow an examination of the influence of the modification on sugar c onformation and tautomeric equilibrium, properties likely to be import ant in understanding the biological consequences of these DNA damage p roducts.