SYNTHESIS AND THERMODYNAMIC STABILITIES OF DAMAGED DNA INVOLVING 8-HYDROXYGUANINE (7,8-DIHYDRO-8-OXOGUANINE) IN A RAS-GENE FRAGMENT

A new building block of 8-hydroxyguanine (7,8-dihydro-8-oxoguanine, oh(8)Gua) with a N-2-(N,N-dimethylaminomethylene) group was prepared for oligonucleotide synthesis. Oligodeoxyribonucleotides corresponding to a part of the human c-Ha-ras gene and containing oh(8)Gua 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 oh(8)Gua:C and oh(8)Gua:A pairs, oh(8)Gua 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.