Nucleic Acids Symposium Series · 2001 · 24 citations · 0 references
PharmacyBiochemistryMolecular BiologyMolecular RecognitionNucleic Acid BiochemistryNucleic Acid ChemistryModified Nucleic AcidsNucleic Acid ModificationNucleic Acid SynthesisNucleobase ChemistryOligonucleotide ChemistryRibonucleic Acid (Rna) ChemistryAntisense Oligonucleotide DesignAntisense RnasConformationally Restricted NucleosidesNucleic Acid Base PairingNucleobase Base PairingOligonucleotide SynthesisRibonucleic Acid (Rna) Structure
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.