1,N2-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. pKa 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 (t1/2 = 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.
Kuśmierek
J T
JT
Division of Cell and Molecular Biology, Donner Laboratory, University of California, Berkeley 94720.
Singer
B
B
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D002254:Carbonates / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004126:Dimethylformamide / Q000737:chemistry; D006868:Hydrolysis; D011119:Polynucleotides / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry
D002254:Carbonates; D011119:Polynucleotides; C054579:1,N(2)-ethenodeoxyguanosine; D004126:Dimethylformamide; D004247:DNA; C037593:potassium carbonate; C004656:chloroacetaldehyde; D003849:Deoxyguanosine; D000079:Acetaldehyde; D011188:Potassium