Bicyclic nucleosides and conformational restriction of oligonucleotides

Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

“…We decided to focus on analogues containing the natural phosphodiester backbone and a bicyclic furanose, hoping to induce enhanced binding affinity towards RNA targets by conformational restriction [6,7]. Molecular modeling revealed 02' to C4' linked analogues as potentially very interesting because of strong conformational restriction, and as a synthetic target we chose the 2~-O,4~--C-methylene-linked ribonucleotide derivatives LNA (Locked Nucleic Acid) [8,9].…”

α-LNA (Locked Nucleic Acid withα-D-Configuration): Synthesis and Selective Parallel Recognition of RNA

“…[10] In general, the most successful approach towards ODNs with high-affinity recognition of complementary nucleic acid sequences has probably been the introduction of conformationally restricted analogues. [1,13,14] Thus, ONs in which the nucleoside monomers contain bi-or tricyclic carbohydrate moieties have been found to display high-affinity binding of, in particular, complementary RNA. [14] The most enhanced properties to date have been obtained with LNA (locked nucleic acid) (Scheme 1).…”

“…[1,13,14] Thus, ONs in which the nucleoside monomers contain bi-or tricyclic carbohydrate moieties have been found to display high-affinity binding of, in particular, complementary RNA. [14] The most enhanced properties to date have been obtained with LNA (locked nucleic acid) (Scheme 1). [15] LNA sequences are defined as ONs that contain one or more LNA monomers, which are nucleosides locked in an N-type conformation due to a bicyclo[2.2.1]heptane carbohydrate skeleton (see the thymine monomer 1; Scheme 1).…”

Synthesis and Thermal Denaturation Studies of Conformationally Restricted 3′‐C‐Ethynyl‐3′‐O,4′‐C‐methyleneribonucleotides

“…In all cases the UV denaturation curves displayed smooth sigmoidal monophasic transitions with a shape similar to curves of unmodified reference duplexes (see Figure S1 in the Supporting InforScheme 1. Reagents and conditions: a) DMTrCl, DMAP, pyridine, room temp., 60 %; b) NC(CH 2 ) 2 OP(Cl)N(iPr) 2 , N,N-diisopropylethylamine, CH 2 Cl 2 , room temp., 86 %; c) DNA-synthesizer; U = uracil-1-yl. mation).…”