Nucleoside derivative and use thereof
View Patent ↗A nucleoside derivative represented below, or a salt thereof. (In (1), R 1 represents a hydrogen atom, a hydroxyl group or a protected group, and in (2), X represent a halogen atom. In (1) and (2), R 2 and R 4 each represent a hydrogen atom, a hydroxyl protecting, phosphate, or protected phosphate group, or —P(═O) n R 5 R 6 (n is 0 or 1, R 5 and R 6 each representing a hydrogen atom, hydroxyl, protected hydroxyl, mercapto, protected mercapto, lower alkoxy, cyano lower alkoxy, amino or substituted amino group, when n is 1, R 5 and R 6 are not both hydrogen atoms), R 3 represents NHR 7 (R 7 represents a hydrogen atom, alkyl, alkenyl or protecting group for an amino group), an azide, amidino or guanidino group, each having a linking group (when R 7 is hydrogen atom, the linking group is an alkylene group), and B represents any of a purine-9-yl, 2-oxo-pyrimidin-1-yl, substituted purine-9-yl or substituted 2-oxo-pyrimidin-1-yl group).
1. An oligonucleotide comprising a nucleoside derivative represented by formula (2) below, or a salt thereof,
wherein:
X represents a fluorine atom,
R 2 and R 4 may be the same or different, and each represents:
a hydrogen atom,
a hydroxyl protecting group,
a phosphate group,
a protected phosphate group, or
—P(═O) n R 5 R 6 in which n is 0 or 1, and R 5 and R 6 may be the same or different, with each representing a hydrogen atom, hydroxyl group, protected hydroxyl group, mercapto group, protected mercapto group, lower alkoxy group, cyano lower alkoxy group, amino group or substituted amino group, but when n is 1, R 5 and R 6 are not both hydrogen atoms,
R 3 represents:
NHR 7 in which R 7 represents a hydrogen atom, an alkyl group, an alkenyl group or a protecting group for an amino group,
an azide group,
an amidino group, or
a guanidino group,
each having a linking group, but when R 7 is hydrogen atom or a protecting group for an amino group, the linking group is an alkylene group which has 2 to 3 carbon atoms, and
B represents a nucleobase.
2. The oligonucleotide of claim 1 , wherein said oligonucleotide is selected from the group consisting of a DNA molecule, a RNA molecule, and a duplex comprising a DNA and/or a RNA molecule.
3. The oligonucleotide of claim 1 , wherein said oligonucleotide comprises a nucleoside derivative represented by the structure:
4. An RNA molecule comprising an oligoribonucleotide derivative represented by formula (2) below, or a salt thereof,
wherein:
X represents a fluorine atom,
R 2 and R 4 may be the same or different, and each represents:
a hydrogen atom,
a hydroxyl protection group,
a phosphate group,
a protected phosphate group, or
—P(═O) n R 5 R 6 in which n is 0 or 1, and R 5 and R 6 may be the same or different, with each representing a hydrogen atom, hydroxyl group, protected hydroxyl group, mercapto group, protected mercapto group, lower alkoxy group, cyano lower alkoxy group, amino group or substituted amino group, but when n is 1, R 5 and R 6 are not both hydrogen atoms,
R 3 represents:
NHR 7 in which R 7 represents a hydrogen atom, an alkyl group, an alkenyl group or a protecting group for an amino group,
an azide group,
an amidino group, or
a guanidino group,
each having a linking group, but when R 7 is hydrogen atom, the linking group is an alkylene group which has 2 to 3 carbon atoms, and
B represents any of a purine-9-yl group, 2-oxo-pyrimidin-1-yl group, substituted purine-9-yl group or substituted 2-oxo-pyrimidin-1-yl group; and
wherein said RNA molecule consists of an RNA interference agent.
5. The RNA molecule of claim 4 , wherein said RNA molecule consists of a siRNA.
6. The RNA molecule according to claim 4 , wherein R 7 represents a hydrogen atom.
7. The RNA molecule according to claim 4 , wherein the nucleoside derivative comprises the structure: