title: Alpha-L-RNA (alpha-L-ribo configured RNA): synthesis and RNA-selective hybridization of alpha-L-RNA/alpha-L-LNA chimera.
abstract: Synthesis of the novel alpha-L-ribofuranosyl phosphoramidite derivative was accomplished via the alpha-L-ribofuranosyl thymine nucleoside. Amidite was used in automated syntheses of chimeric oligonucleotides composed of mixtures of the novel alpha-L-RNA nucleotide monomer ((alphaL)T, alpha-L-ribo configured RNA), and DNA, LNA (T(L), locked nucleic acid) or alpha-L-LNA ((alphaL)T(L), alpha-L-ribo configured locked nucleic acid) nucleotide monomers. For alpha-L-RNA/DNA and alpha-L-RNA/alpha-L-LNA chimeras, RNA-selective hybridization was obtained, for alpha-L-RNA/alpha-L-LNA chimera we found increased binding affinity compared to the corresponding DNA:RNA reference duplex. In addition, alpha-L-RNA/alpha-L-LNA chimera displayed significant stabilization towards 3'-exonucleolytic degradation. These results indicate that alpha-L-RNA/alpha-L-LNA chimeras deserve further evaluation as antisense molecules.
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100, Copenhagen, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Keinicke
authors.forename: Mads D
authors.initials: MD
authors.lastname: Sørensen
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
mesh_terms: D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization / Q000379:methods*; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D012313:RNA / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D009843:Oligoribonucleotides; D020320:Oligoribonucleotides, Antisense; D012313:RNA