Identification and characterization of a reaction product of 2'-deoxyoxanosine with glycine.

Abstract

2'-Deoxyoxanosine (dOxo) is a novel DNA lesion produced from dGuo by reaction with nitrous acid or nitric oxide [Suzuki, T., Yamaoka, R., Nishi, M., Ide, H., and Makino, K. (1996) J. Am. Chem. Soc. 118, 2515-2516]. We investigated the reaction of dOxo with glycine (Gly) under physiological conditions. When 5 mM dOxo was incubated with 500 mM Gly in 100 mM sodium phosphate buffer (pH 7.4) at 37 degrees C, an unknown product was formed exclusively. The yield of the product was 86% at an incubation time of 3 h. Using spectrometric data, it was identified as a ring-opened adduct containing an amide bond between the carbonyl group of dOxo and the amino group of Gly. The adduct was very stable (t(1/2) = 1280 h) under physiological conditions. Furthermore, dOxo in oligodeoxynucleotide reacted with Gly, yielding the same adduct. These results suggest that dOxo formed in DNA may react with Gly present in cells, resulting in adduct formation in vivo.