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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
2'-O,4'-C-ethylene-bridged nucleic acids (ENA) with nuclease-resistance and high affinity for RNA
K Morita1, C Hasegawa, M Kaneko
1Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo 140-8710, Japan.
Abstract:
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,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA), restricts the sugar puckering to the N-conformation. The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (delta Tm = degrees C/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.
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