Oligonucleotide end caps
Modified nucleic acids are described herein, including pharmaceutical compositions comprising the modified nucleic acids, and methods of using the modified nucleic acids.
1. An oligonucleotide comprising a nucleosidic end cap of one of the following formulas:
wherein:
J is an ether linkage;
K is O;
B 1 and B 2 are each independently a natural or modified nucleobase;
X is H, OH, OM, SH, SM, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylamino, or optionally substituted dialkylamino, where M represents independently for each occurrence an alkali metal or a transition metal with an overall charge of +1;
Z 10 is O;
Y 10 is O;
R and R 2 are each independently H, OH, SH, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylamino, or optionally substituted dialkylamino;
s is 1; and
2. The oligonucleotide of claim 1 , wherein:
R is H, OH, OMe, F, or O(CH 2 ) 2 OMe; and
R 2 is OH, F, C 1 -C 32 alkyl, C 1 -C 32 alkoxy, —(CH 2 ) n —NR b R c ,—O(CH 2 ) n —NR b R c ,—[O(CH 2 ) r ] m—OR b , —[O(CH 2 ) r ] m —NR b R c , —(CH 2 ) n —O—NR b R c , —O—(CH 2 ) n —O—NR b R c , —[O(CH 2 ) r ] m —O—NR b R c , —(CH 2 ) n —N(R b )—C(═NR b )—NR b R c , —O—(CH 2 ) n —NR b —C(═NR b )—NR b R c , —[O(CH 2 ) r ] m —N(R b )—C(═NR b )—NR b R c , —(CH 2 ) n —O—NR b —C(═NR b )—NR b R c , —O—(CH 2 ) n —O—NR b —C(═NR b )—NR b R c , or —[O(CH 2 ) r ] m —O—NR b —C(═NR b )—NR b R c , where R b and R c are each independently hydrogen or C 1 -C 32 alkyl, and n, m and r are each independently an integer from 1-20.
3. The oligonucleotide of claim 1 , wherein said oligonucleotide is single-stranded siRNA.
4. The oligonucleotide of claim 1 , wherein said oligonucleotide is double-stranded siRNA.
5. The oligonucleotide of claim 1 , wherein B 2 is
wherein Y is H or CH 3 .
6. The oligonucleotide of claim 5 , wherein B 2 is
7. The oligonucleotide of claim 5 , wherein B 2 is
8. The oligonucleotide of claim 1 , wherein B 1 is adenine, guanine,
wherein Y is H or CH 3 .
9. The oligonucleotide of claim 8 , wherein B 1 is adenine.
10. The oligonucleotide of claim 8 , wherein B 1 is guanine.
11. The oligonucleotide of claim 1 , wherein B 1 is
12. The oligonucleotide of claim 1 , wherein B 1 is
13. The oligonucleotide of claim 1 , wherein the nucleosidic end cap is a compound selected from the group consisting of: