2′-O, 4′-C-Ethylene-bridged nucleic acids (ENA) with nuclease-resistance and high affnity for RNA

Novel nucleosides, 2'-O,4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks for antisense oligonucleotides. The 2'-O,4'-C-ethylene linkage of these nucleosides, as well as the linkage of 2'-O,4C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA), restricts the sugar puckering to the Nconformation. The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand ( A Tm = +5 V I modification) and were approximately 400 and 80 times more nuclease-resistant than natural DNA and BNA/LNA, respectively. These results indicate that ENA have better antisense activity than BNA/LNA.