title: Synthesis and structural characterization of 2'-fluoro-α-L-RNA-modified oligonucleotides.
abstract: We describe the synthesis and binding properties of oligonucleotides that contain one or more 2'-fluoro-α-L-RNA thymine monomer(s). Incorporation of 2'-fluoro-α-L-RNA thymine into oligodeoxynucleotides decreased thermal binding stability slightly upon hybridization with complementary DNA and RNA with the smallest destabilization towards RNA. Thermodynamic data show that the duplex formation with 2'-fluoro-α-L-RNA nucleotides is enthalpically disfavored but entropically favored. 2'-Fluoro-α-L-RNA nucleotides exhibit very good base pairing specificity following Watson--Crick rules. The 2'-fluoro-α-L-RNA monomer was designed as a monocyclic mimic of the bicyclic α-L-LNA, and molecular modeling showed that this indeed is the case as the 2'-fluoro monomer adopts a C3'-endo/C2'-exo sugar pucker. Molecular modeling of modified duplexes show that the 2'-fluoro-α-L-RNA nucleotides partake in Watson--Crick base pairing and nucleobase stacking when incorporated in duplexes while the unnatural α-L-ribo configured geometry of the sugar is absorbed by changes in the sugar-phosphate backbone torsion angles. The duplex behavior of our new nucleotide follows that of α-L-LNA, by and large.
authors: Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors: Troels
authors: T
authors: Bundgaard Jensen
authors: Anna
authors: A
authors: Pasternak
authors: Andreas
authors: A
authors: Stahl Madsen
authors: Michael
authors: M
authors: Petersen
authors: Jesper
authors: J
authors: Wengel
mesh_terms: D020029:Base Pairing; D001671:Biochemistry / Q000379:methods*; D001688:Biological Products / Q000032:analysis / Q000138:chemical synthesis*; D002942:Circular Dichroism; D018076:DNA, Complementary / Q000737:chemistry* / Q000378:metabolism; D004355:Drug Stability; D054879:Halogenation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000032:analysis / Q000138:chemical synthesis*; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001688:Biological Products; D018076:DNA, Complementary; D009841:Oligonucleotides; C477371:locked nucleic acid; D012313:RNA