Oligonucleotide end caps

1. An oligonucleotide comprising a nucleosidic end cap represented by formula (Ib) or formula (IIb):

wherein:

J is an ether, sulfide, amino, ester, sulfonamide, amide, urea, carbamate, or a phosphorus-containing linkage;

K is independently O, S, NR′, or optionally substituted alkyl;

R′ is hydrogen, acyl, or unsubstituted or substituted aliphatic;

B 1 is independently a natural or modified nucleobase;

X 10 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, S, or NR′;

R, R 1 , R 2 , and R 3 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;

R 4 is hydrogen, optionally substituted alkyl, optionally substituted acyl, or optionally substituted sulfonamide; and

s is an integer from 0-7.

2. The oligonucleotide of claim 1 , wherein the nucleosidic end cap is represented by formula (Ic) or formula (IIc):

wherein:

B 1 is a natural or modified nucleobase;

R is H, OH, OMe, F, or O(CH 2 ) n (Z)(CH 2 ) m —H, where n is 1-20, m is 0-20, and Z is O or S;

X 10 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, S, or NR′, where R′ is hydrogen, acyl, or unsubstituted or substituted aliphatic;

R 1 , R 2 and R 3 are each independently H, F, hydroxyl, alkoxy, amino, alkylamimo, or dialkylamino; and

R 4 is hydrogen, C 1 -C 32 alkyl, —C(X)—(CH 2 ) n —H, —C(X 1 )Y 1 —(CH 2 ) n —H, —C(X 1 )N(R b )—(CH 2 ) n —H, —(CH 2 ) n —NR b R c , —C(X 1 )—(CH 2 ) n —NR b R c , —C(X 1 )Y 1 —(CH 2 ) n —NR b R c , —C(X 1 )N(R b )—(CH 2 ) n —NR b R c , —(CH 2 ) n —N(R b )—C(═NR b )—NR b R c , —C(X 1 )—(CH 2 ) n —N(R b )—C(═NR b )—NR b R c , —C(X 1 )Y 1 —(CH 2 ) n —N(R b )—C(═NR b )—NR b R c or —C(X 1 )N(R b )—(CH 2 ) n —N(R b )—C(═NR b )—NR b R c , where n is 1-20; m is 0-20; X 1 is O or S; Y 1 is absent, O, or N(R b ), and each R b and R c is independently hydrogen or C 1 -C 32 alkyl.

3. An oligonucleotide comprising a nucleosidic end cap represented by formula (Id) or formula (IId):

wherein:

B 1 is a natural or modified nucleobase;

R is H, OH, OMe, F, or O(CH 2 ) n (Z)(CH 2 ) m —H, where n is 1-20, m is 0-20, and Z is O or S;

X and X 10 are each independently 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 independently O, S, or NR′;

R′ is hydrogen, acyl, unsubstituted or substituted aliphatic;

R 1 , R 2 and R 3 are each independently H, F, hydroxyl, alkoxy, amino, alkylamimo, or dialkylamino; and

R 4 is hydrogen, C 1 -C 32 alkyl, —C(X)—(CH 2 ) n —H, —C(X 1 )Y 1 (CH 2 ) n —H, —C(X 1 )N(R b )—(CH 2 ) n —H, —(CH 2 ) n —NR b R c , —C(X 1 )—(CH 2 ) n —NR b R c , —C(X 1 )Y 1 (CH 2 ) n —NR b R c , —C(X 1 )N(R b )—(CH 2 ) n —NR b R c , —(CH 2 ) n —N(R b )—C(═NR b )—NR b R c , —C(X 1 )—(CH 2 ) n —N(R b )—C(═NR b )—NR b R c , —C(X 1 )Y 1 —(CH 2 ) n —N(R b )—C(═NR b )—NR b R c or —C(X 1 )N(R b )—(CH 2 ) n —N(R b )—C(═NR b )—NR b R c , where n is 1-20; m is 0-20; X 1 is O or S; Y 1 is absent, O, or N(R b ), and each R b and R c is independently hydrogen or C 1 -C 32 alkyl.

4. An oligonucleotide comprising a nucleosidic end cap represented by formula (IIIc) or formula (IIId):

wherein:

B 1 is independently a natural or modified nucleobase;

X 10 is independently 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 independently O, S, or NR′;

R′ is hydrogen, acyl, or unsubstituted or substituted aliphatic;

R, R 2 and R 3 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; and

R 4 is hydrogen, optionally substituted alkyl, optionally substituted acyl, or optionally substituted sulfonamide.

5. An oligonucleotide comprising a nucleosidic end cap represented by formula (IIIe) or formula (IIIf):

wherein:

B 1 is a natural or modified nucleobase;

X 10 is independently 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 independently O, S, or NR′

R′ is hydrogen, acyl, or unsubstituted or substituted aliphatic;

R, R 2 , and R 3 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;

R 4 is hydrogen, optionally substituted alkyl, optionally substituted acyl, or optionally substituted sulfonamide.

6. The oligonucleotide of claim 1 , wherein said oligonucleotide is single-stranded siRNA.

7. The oligonucleotide of claim 1 , wherein said oligonucleotide is double-stranded siRNA.

8. The oligonucleotide of claim 3 , wherein said oligonucleotide is single-stranded siRNA.

9. The oligonucleotide of claim 3 , wherein said oligonucleotide is double-stranded siRNA.

10. The oligonucleotide of claim 4 , wherein said oligonucleotide is single-stranded siRNA.

11. The oligonucleotide of claim 4 , wherein said oligonucleotide is double-stranded siRNA.

12. The oligonucleotide of claim 5 , wherein said oligonucleotide is single-stranded siRNA.

13. The oligonucleotide of claim 5 , wherein said oligonucleotide is double-stranded siRNA.