L-ribo-lna analogues

C - Chemistry – Metallurgy – 07 – H

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C07H 19/04 (2006.01) A61K 31/70 (2006.01) C07H 19/06 (2006.01) C07H 19/16 (2006.01) C07H 21/00 (2006.01) C12P 19/34 (2006.01)

Patent

CA 2372085

Nucleoside analogues wherein a 2'-4'-bridge locks the conformation of the nucleoside have been synthesised with an inverted stereochemistry at C-3' and C-4' to provide the L-ribo- configurated LNA nucleoside. The synthesis of L-ribo-LNA--nucleoside is applicable to all nucleobases including thymine, adenine, cytosine, guanine and uracil. These Locked Nucleic Acids (LNAs) with L-ribo-configuration have been utilised in the synthesis of 2'-0- 4'-C-methylene-.alpha.-L-ribofuranosyl nucleotides as well as oligonucleotides with L-ribo-LNA nucleosides included therein. Methods of targeting complementary nucleic acids are greatly improved by use of these L-ribo-LNA modified oligonucleotides due to their high affinity for complementary nucleic acids.

Selon l'invention, des analogues de nucléoside, dans lesquels un pont 2'-4' verrouille la conformation du nucléoside, ont été synthétisés par stéréochimie inversée aux niveaux C-3' et C-4' de manière à former le nucléoside LNA à structure L-ribo. La synthèse du nucléoside L-ribo-LNA est applicable à toutes les nucléobases, telles que la thymine, l'adénine, la cytosine, la guanine et l'uracile. Ces acides nucléiques verrouillés (LNA) à structure L-ribo ont été utilisés dans la synthèse de nucléotides 2'-O-4'-C-méthylène- alpha -L-ribofuranosyle et d'oligonucléotides comprenant des nucléosides L-ribo-LNA. Les procédés de ciblage d'acides nucléiques complémentaires sont nettement améliorés grâce à l'utilisation de ces oligonucléotides modifiés L-ribo-LNA, étant donné leur grande affinité avec lesdits acides nucléiques complémentaires.

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