Formation of s-triazines during aerial oxidation of 8-oxo-7,8-dihydro-2 '-deoxyguanosine in concentrated ammonia

After automated DNA synthesis, oligodeoxynucleotides containing 8-oxoguanin e are sensitive to aerial oxidation when subjected to the basic conditions necessary for deprotection and release of the oligomer from the control por e glass support. The major oxidation products of this heterocyclic moiety h ave been characterized by permitting 8-oxo-7,8-dihydro-2'-deoxyguanosine to react with oxygen in the presence of 28% aqueous ammonia at room temperatu re. Products were isolated by reverse phase HPLC and analyzed by electrospr ay ionization-mass spectrometry and gas chromatography-mass spectrometry of the trimethylsilyl-derivatives. 2-Amino-4-hydroxy-s-triazine-6-carboxylic acid and 2-amino-4-hydroxy-6-carbamyl-s-triazine were identified by these t echniques and standards were synthesized. In addition, GC-MS analysis revea led other oxidation products, including urea, guanidine and 2-deoxyribose, which were not observed by HPLC because these compounds are transparent in the UV region of the spectrum. Both s-triazines were also observed when a p urified, synthetic oligodeoxynucleotide containing a single 8-oxoguanine mo iety was exposed to the same conditions. Oxidation of 8-oxoguanine appears to parallel the uric acid oxidation pathway, and a mechanistic scheme is pr oposed to account for the products of degradation.