Synthesis and Thermodynamic Stabilities of Damaged DNA Involving 8-Hydroxyguanine (7,8-Dihydro-8-Oxoguanine) in a ras-Gene Fragments

Abstract

A new building block of 8-hydroxyguanine (7,8-dihydro-8-oxoguanine, oh⁸Gua) with a N²-(N, N-dimethylaminomethylene) group was prepared for oligonucleotide synthesis. Oligodeoxyribonucleotides corresponding to a part of the human c-Ha-ras gene and containing oh⁸Gua in codon 12 were synthesized using the phosphoramidite monomer. The oligonucleotides were used for thermal denaturation studies and circular dichroism measurements. Thermodynamic parameters showed that, other than oh⁸Gua:C and oh⁸Gua:A pairs, oh⁸Gua at the first and second positions of codon 12 forms stable pairs with G and T, respectively. These results may explain the different spectra of mutations induced by the base at the first and second positions of codon 12.