Coupling products of nucleosides with the glyoxal adduct of deoxyguanosine.
Glyoxal is a widely dispersed environmental mutagen that reacts with DNA and deoxyguanosine to give primarily the 1,N(2)-guanine adduct, i.e., 3-(2'-deoxy-beta-d-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purin-9-one. Kasai et al. have reported [Kasai, et al. (1998) Carcinogenesis 19, 1459-1465] additional minor reactions of glyoxal to give bis-nucleosides of unknown structure involving glyoxal conjugation of dG with dA, dC, and dG itself. Reaction conditions have been modified to give large increases in the yields of the adducts, which has permitted structural characterization utilizing chemical and spectroscopic techniques. The glyoxal conjugates of dG with dA and dC are imidazo[1,2-a]purines involving displacement of the 6-hydroxyl group of the dG conjugate by the exocyclic amino groups of dA and dC. The dG conjugate is a symmetrical fusion of two imidazo[1,2-a]purines in which both the 6- and the 7-hydroxyl groups of the dG conjugate have been replaced. The glyoxal conjugates are formed as pairs of diastereomers. The dC and dA have a trans orientation of substituents at C6 and C7; the adduct of dG has a cis orientation. The absolute configurations of the individual diastereomers have been tentatively assigned based on comparison of their CD spectra with configurationally assigned diastereomers of the crotonaldehyde adduct of deoxyguanosine.
Brock
Angela K
AK
Department of Chemistry, Center in Molecular Toxicology, Institute of Chemical Biology, Vanderbilt University, Box B-1715, Vanderbilt University, Nashville, Tennessee 37235, USA.
Kozekov
Ivan D
ID
Rizzo
Carmelo J
CJ
Harris
Thomas M
TM
D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry / Q000378:metabolism; D003853:Deoxyribonucleosides / Q000737:chemistry*; D006037:Glyoxal / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
D018736:DNA Adducts; D003853:Deoxyribonucleosides; D006037:Glyoxal; D003849:Deoxyguanosine