title: Synthesis of N2,3-ethenodeoxyguanosine, N2,3-ethenodeoxyguanosine 5'-phosphate, and N2,3-ethenodeoxyguanosine 5'-triphosphate. Stability of the glycosyl bond in the monomer and in poly(dG,epsilon dG-dC).
abstract: The synthesis of a new modified etheno-2'-deoxyguanosine is reported. N2,3-Ethenodeoxy-guanosine (epsilon dGuo) is a product in double-stranded DNA treated with the carcinogen vinyl chloride in vivo or its metabolite chloroacetaldehyde in vitro. The lability of its glycosyl bond has, however, interfered with its isolation from DNA. The synthesis, starting with O6-benzyl-2'-deoxyguanosine 5'-phosphate, reacted with bromoacetaldehyde, could only be accomplished in slightly alkaline media, which prevented significant loss of the sugar. The 5'-phosphate also decreased the lability of the glycosyl bond. The resulting compound, when deprotected, was converted to N2,3-ethenodeoxyguanosine 5'-triphosphate, as well as the corresponding nucleoside. Fluorescence, UV, and 1H NMR data were consistent with the assigned structures and almost identical with those of the previously synthesized much more stable ribo analogues [Kuśmierek et al. (1987) J. Org. Chem. 52, 2374-2378]. A systematic study of the pH-dependent glycosyl bond cleavage gave a t1/2, 37 degrees C, pH 6, of approximately 3.5 h for the nucleoside and 7-10 h for the nucleotides. Comparison, under the same conditions, of stability of the glycosyl bond in poly(dG,epsilon dG-dC) showed an increased stability of 2 orders of magnitude, t1/2 = approximately 600 h. The rate of sugar loss was, in all cases, greatly decreased at higher pH's, over the range of pH 5-9. These stability data indicate that when slightly alkaline conditions can be used, studies on incorporation of epsilon dGuo into polymers for in vitro mutagenesis studies are possible.
authors.affiliation: Donner Laboratory, University of California, Berkeley 94720.
authors.forename: J T
authors.initials: JT
authors.lastname: Kuśmierek
authors.forename: W
authors.initials: W
authors.lastname: Folkman
authors.forename: B
authors.initials: B
authors.lastname: Singer
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives; D002851:Chromatography, High Pressure Liquid; D003848:Deoxyguanine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D011089:Polydeoxyribonucleotides / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D003848:Deoxyguanine Nucleotides; D011089:Polydeoxyribonucleotides; C072469:N(2),3-ethenodeoxyguanosine 5'-phosphate; C079486:N(2),3-ethenodeoxyguanosine; C068266:N(2),3-etheneodeoxyguanosine-5'-triphosphate; C019530:poly(dC-dG); C004656:chloroacetaldehyde; D003849:Deoxyguanosine; D000079:Acetaldehyde