α- -RNA (α- -ribo Configured RNA): Synthesis and RNA-Selective Hybridization of α- -RNA/α- -LNA Chimera

Synthesis of the novel α- -ribofuranosyl phosphoramidite derivative 7 was accomplished via the α- -ribofuranosyl thymine nucleoside 4. Amidite 7 was used in automated syntheses of chimeric oligonucleotides composed of mixtures of the novel α- -RNA nucleotide monomer (αLT, α- -ribo configured RNA), and DNA, LNA (TL, locked nucleic acid) or α- -LNA (αLTL, α- -ribo configured locked nucleic acid) nucleotide monomers. For α- -RNA/DNA and α- -RNA/α- -LNA chimeras, RNA-selective hybridization was obtained, for α- -RNA/α- -LNA chimera we found increased binding affinity compared to the corresponding DNA:RNA reference duplex. In addition, α- -RNA/α- -LNA chimera displayed significant stabilization towards 3′-exonucleolytic degradation. These results indicate that α- -RNA/α- -LNA chimeras deserve further evaluation as antisense molecules.