Depurination and imidazole ring-opening in nucleosides and DNA alkylated by styrene oxide.
Styrene-7,8-oxide was reacted with guanosine and deoxyguanosine and four isomeric 7-alkylguanosines were isolated, two of each being substitutions through the alpha and beta carbon of styrene oxide. The diastereomeric adducts imidazole ring-opened at an identical rate but the alpha- and beta-adducts differed (half-lives 90 and 56 min, respectively, pH 10, 24 degrees C). The 7-beta alkyl-deoxyguanosine derivatives ring-opened at a six times slower rate, which was similar to 7-methyldeoxyguanosine. The diastereomeric guanosine products also depurinated at the same rate but the beta-derivatives depurinated faster than the alpha-derivatives (t1/2 35 vs. 79 min, respectively, pH 1, 70 degrees C). The differences in the ring-opening and depurination of the alpha- and beta-isomers corresponded to their respective pK alpha values (7.31-7.32 vs. 7.16-7.19). The 7-alkyldeoxyguanosine derivatives of styrene oxide depurinated equally fast as 7-methyldeoxyguanosine. By contrast, the depurination of 7-alkylguanine was 15 times slower in the single-stranded DNA and 55 times slower in the double-stranded DNA.
Vodicka
P
P
Institute of Occupational Health, Helsinki, Finland.
Hemminki
K
K
D000478:Alkylation; D002851:Chromatography, High Pressure Liquid; D004247:DNA; D003849:Deoxyguanosine / Q000031:analogs & derivatives; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D006151:Guanosine / Q000031:analogs & derivatives; D006207:Half-Life; D007093:Imidazoles; D009705:Nucleosides; D011687:Purines; D013237:Stereoisomerism
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D007093:Imidazoles; D009705:Nucleosides; D011687:Purines; D006151:Guanosine; D004247:DNA; C013690:styrene oxide; D003849:Deoxyguanosine