1,N-2-ETHENODEOXYGUANOSINE - PROPERTIES AND FORMATION IN CHLOROACETALDEHYDE-TREATED POLYNUCLEOTIDES AND DNA

1,N2-Etheno-2'-deoxyguanosine (1,N2-epsilon-dGuo), not previously reported as a product of chloroacetaldehyde (CAA) reaction, has been synthesized and characterized. Reaction of deoxyguanosine with CAA in dimethylformamide in the presence of K2CO3 led to preparation of pure 1-N2-epsilon-dGuo with 55% yield. pK(a) values are 2.2 and 9.2. The anionic form of the compound exhibits weak but defined fluorescence; the intensity is similar to that of N2,3-etheno-2'-deoxyguanosine (N2,3-epsilon-dGuo) at neutrality. The stability of the glycosyl bond of 1-N2-epsilon-dGuo (tl/2 = 2.3 h at 37-degrees-C, pH 1) is 10-fold greater than of unmodified deoxyguanosine and at least one thousand-fold greater than of isomeric N2,3-epsilon-dGuo. Reaction of CAA with model polynucleotides indicates that hydrogen bonding of guanine residues in the double-stranded structures is, as expected, an important factor in the formation of 1-N2-ethenoguanine. In contrast, the formation of isomeric N2,3-ethenoguanine is relatively independent of whether the DNA is single-or double-stranded. In salmon sperm DNA, reacted with CAA at neutrality, the formation of 1-N2-ethenoguanine could be demonstrated. However, we find the efficiency of formation of this adduct in double-stranded DNA to be lower than that of all other etheno derivatives.