Synthesis and Properties of Oligonucleotides Containing 2′-O,4′-C-Methyleneoxy-Bridged Pyrimidine Derivatives

In this study, 2'-O,4'-C-methyleneoxy-bridged nucleic acid, a unique consecutive three-acetal-containing nucleic acid (TaNA), was designed. Pyrimidine derivatives of methylated TaNA (Me-TaNA) were also synthesized and introduced into oligonucleotides via solid-phase synthesis. The Me-TaNA-modified oligonucleotides exhibited higher stabilities when forming duplexes with single-stranded RNA or triplexes with double-stranded DNA, relative to the natural oligonucleotides and modified oligonucleotides containing another 2',4'-bridged 5-methyluridine, such as 2',4'-BNA/LNA and 2',4'-ENA. Furthermore, Me-TaNA within oligonucleotides significantly enhanced nuclease resistance.

Automated summary

In this study, a unique consecutive three-acetal-containing nucleic acid (TaNA) was designed and its methylated derivatives were synthesized. The modified oligonucleotides showed higher stability when forming duplexes or triplexes compared to natural and other modified oligonucleotides, and also exhibited enhanced nuclease resistance.