CHARACTERIZATION AND CHEMICAL-STABILITY OF PHOTOOXIDIZED OLIGONUCLEOTIDES THAT CONTAIN TA-D-ERYTHRO-PENTOFURANOSYL)AMINO]-5(2H)-OXAZOLONE

The chemical insertion of ta-D-erythro-pentofuranosyl)amino]-5(2H)-oxa zolone (oxazolone), a major oxidation compound of 2'-deoxyguanosine, i nto oligonucleotides is a challenging issue, due to the high alkali la bility of the lesion. This difficulty was overcome by the specific rib oflavin-mediated photosensitization of a central guanine residue in DN A fragments. The modified 9-mer thus prepared, was purified by reverse HPLC and characterized by electrospray ionization mass spectrometry. Additional structural information was gained from the assignment of en zymatic hydrolysates of the oxidized DNA fragment. The high alkali lab ility of the oxazolone-containing DNA fragment was inferred from seque nce gel analysis. In contrast, a similar 9-mer that contains 8-oxo-7,8 -dihydro-2'-deoxyguanosine in place of the oxazolone was fully stable under the conditions of piperidine treatment.