Modified nucleic acid monomer compound and oligonucleic acid analog
The present invention provides a modified nucleic acid monomer compound having a specific backbone such as 2-ethylglycerol or methoxymethyl-1,3-propanediol backbone instead of a ribose or deoxyribose backbone of a nucleoside, and an oligonucleic acid analogue containing the monomer compound as at least one of building blocks. The oligonucleic acid analogue containing the nucleic acid monomer compound of the present invention allows provision of an oligonucleic acid analogue having excellent biological stability and/or target gene silencing activity.
1. An oligonucleic acid analogue comprising one or more partial structures represented by the following formula (IX) or a salt thereof,
wherein:
B 3 represents a nucleobase; and
L represents —OCH 2 CH 2 — or —CH 2 OCH 2 —; provided that when two or more partial structures are included, B 3 and L in the partial structures may be respectively the same or different.
2. The oligonucleic acid analogue according to claim 1 or a salt thereof, wherein B 3 is a nucleobase selected from the following formulae (II)′, (III)′, (IV)′ and (V)′:
wherein:
R 1 represents a hydrogen atom or methyl;
R 2 and R 4 each independently represent a hydrogen atom, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 alkenyl, C 3-6 alkynyl, C 1-6 alkyl-carbonyl, C 1-6 alkylsulphonyl, C 6-14 aryloxy-carbonyl, C 6-14 aryl-carbonyl, C 6-14 arylsulphonyl or a protective group; and
R 3 , R 5 and R 6 each independently represent a hydrogen atom, C 1-6 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, C 1-6 alkyl-carbonyl, C 1-6 alkylsulphonyl, C 6-14 aryloxy-carbonyl, C 6-14 aryl-carbonyl, C 6-14 arylsulphonyl or a protective group.
3. The oligonucleic acid analogue according to claim 2 or a salt thereof, wherein the protective groups in R 2 , R 3 , R 5 and R 6 are each independently selected from a carbamate protective group, an acyl protective group, an imide protective group and a benzyl protective group, and
the protective group in R 4 is selected from a silyl protective group, a trityl protective group, a heterocyclic protective group, a benzyl protective group, an aliphatic acyl protective group, an aromatic acyl protective group, an ether protective group, a carbamoyl protective group and an alkoxycarbonyl protective group.
4. The oligonucleic acid analogue according to claim 2 or a salt thereof, wherein B 3 is selected from the following formulae (X), (XI), (XII) and (XIII):
wherein R 1 is as defined above.
5. The oligonucleic acid analogue according to claim 2 or a salt thereof, wherein L is —OCH 2 CH 2 —.
6. The oligonucleic acid analogue according to claim 2 or a salt thereof, wherein the oligonucleic acid analogue contains 4 to 100 nucleobase units in total per strand.
7. The oligonucleic acid analogue according to claim 2 or a salt thereof, wherein the oligonucleic acid analogue contains 4 to 30 nucleobase units in total per strand.