Synthesis of purine derivatives of Me-TaNA and properties of Me-TaNA-modified oligonucleotides

We previously reported that pyrimidine derivatives of methylated 2 '-O,4 '-C-methyleneoxy-bridged nucleic acid (Me-TaNA), a unique consecutive three-acetal-containing nucleic acid, are promising building blocks for chemically modified oligonucleotides. Herein, purine derivatives of Me-TaNA (Me-TaNA-A and -G) were synthesized and introduced into oligonucleotides. During the synthesis, we found stereoselective introduction of a substituent on the 4 ' carbons by using 2 ',3 '-carbonate compounds as substrates. When forming duplexes with single-stranded RNA, the modified oligonucleotides, including purine derivatives of Me-TaNA, showed higher duplex stability than the natural oligonucleotide. This study enabled the use of Me-TaNA for the chemical modification of various oligonucleotide sequences because synthesis of Me-TaNAs with all four nucleobases was achieved.

Automated summary

The pyrimidine derivatives of methylated 2'-O,4'-C-methyleneoxy-bridged nucleic acid (Me-TaNA), a unique consecutive three-acetal-containing nucleic acid, have been shown to be promising building blocks for chemically modified oligonucleotides. In this study, purine derivatives of Me-TaNA (Me-TaNA-A and -G) were synthesized and introduced into oligonucleotides. The modified oligonucleotides, including purine derivatives of Me-TaNA, exhibited increased duplex stability compared to natural oligonucleotides when forming duplexes with single-stranded RNA.