Oligonucleotides comprising a non-phosphate backbone linkage

C - Chemistry – Metallurgy – 07 – H

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Details

C07H 21/00 (2006.01) A61K 31/7088 (2006.01) A61K 48/00 (2006.01) A61P 25/00 (2006.01) A61P 29/00 (2006.01) A61P 31/00 (2006.01) A61P 33/00 (2006.01) A61P 35/00 (2006.01) A61P 37/02 (2006.01) C07H 19/00 (2006.01) C07H 19/04 (2006.01) C07H 19/073 (2006.01) C07H 19/173 (2006.01)

Patent

CA 2572151

One aspect of the present invention relates to a ribonucleoside substituted with a phosphonamidite group at the 3~-position. In certain embodiments, the phosphonamidite is an alkyl phosphonamidite. Another aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a non-phosphate linkage occurs in only one strand. In certain embodiments, a non-phosphate linkage occurs in both strands. In certain embodiments, a ligand is bound to one of the oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, a ligand is bound to both of the oligonucleotide strands comprising the double- stranded oligonucleotide. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one non-phosphate linkage. Representative non-phosphate linkages include phosphonate, hydroxylamine, hydroxylhydrazinyl, amide, and carbamate linkages. In certain embodiments, the non-phosphate linkage is a phosphonate linkage. In certain embodiments, a ligand is bound to the oligonucleotide strand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety.

Un aspect de l'invention concerne un ribonucléoside substitué par un groupe phosphonamidite en position 3'. Dans certains modes de réalisation, le phosphonamidite est un phosphonamidite d'alkyle. Un autre aspect de l'invention concerne un oligonucléotide double brin comprenant au moins une liaison non-phosphate. Les liaisons non-phosphate représentatives sont entre autres des liaisons phosphonate, hydroxylamine, hydroxylhydrazinyle, amide et carbamate. Dans certains modes de réalisation, la liaison non-phosphate est une liaison phosphonate. Dans certains modes de réalisation, une liaison non-phosphate apparaît dans seulement un brin. Dans certains modes de réalisation, un ligand est lié à un des brins de l'oligonucléotide comprenant l'oligonucléotide double brin. Dans certains modes de réalisation, un ligand est lié aux deux brins d'oligonucléotide comprenant l'oligonucléotide double brin. Dans certains modes de réalisation, les brins d'oligonucléotide comprennent au moins un fragment sucre modifié. Un autre aspect de l'invention concerne un oligonucléotide simple brin comprenant au moins une liaison non phosphate. Les liaisons non-phosphate représentatives sont, entre autres, les liaisons phosphonate, hydroxylamine, hydroxylhydrazinyle, amide et carbamate. Dans certains modes de réalisation, la liaison non phosphate est une liaison phosphonate. Dans certains modes de réalisation, un ligand est lié au brin d'oligonucléotide. Dans certains modes de réalisation, l'oligonucléotide comprend au moins un fragment sucre modifié.

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