Depurination and imidazole ring-opening in nucleosides and DNA alkylated by styrene oxide

Chem Biol Interact. 1988;68(1-2):117-26. doi: 10.1016/0009-2797(88)90010-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Chromatography, High Pressure Liquid
  • DNA*
  • Deoxyguanosine / analogs & derivatives
  • Epoxy Compounds*
  • Ethers, Cyclic*
  • Guanosine / analogs & derivatives
  • Half-Life
  • Imidazoles*
  • Nucleosides*
  • Purines*
  • Stereoisomerism

Substances

  • Epoxy Compounds
  • Ethers, Cyclic
  • Imidazoles
  • Nucleosides
  • Purines
  • Guanosine
  • DNA
  • styrene oxide
  • Deoxyguanosine