Methylated DNA: The influence of 7-deaza-7-methylguanine on the structure and stability of oligonucleotides

The 7-deaza-2'-deoxy-7-methylguanosine (2b) [9], which is the glycosylic-bond-stable, noncharged analogue of 2'-deoxy-7-methylguanosine (1b), was incorporated in DNA by solid-phase synthesis. As building blocks, the protected phosphonate 3a and the phosphoramidite 3b were prepared. The 7-methyl group of 2b stabilizes the B-DNA duplex compared to 7-deaza-2'-deoxyguanosine but does not induce a B-Z transition as it is known from compound 1b. The stabilization by the 7-deaza-7-methylguanine moiety is sequence-dependent, and the nearest-neighbor influence is different from that of 7-deazaguanine. Homooligonucleotides of 2b show sigmoidal melting indicating a highly ordered single-stranded structure. In general, oligonucleotides containing 2b are very stable against hydrolysis with calf-spleen phosphodiesterase (CS-PDE, 5' --> 3' exonuclease), while phosphodiester hydrolysis with snake-venom phosphodiesterase (SV-PDE, 3' --> 5' exonuclease) is only slightly reduced.