Amine-derivatized nucleosides and oligonucleosides
AssigneeIsis Pharmaceuticals, Inc.
InventorsPhillip Dan Cook, Muthiah Manoharan, Charles J. Guinosso
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Abstract
Nucleosides and oligonucleosides functionalized to include alkylamino functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steriods, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosided through the alkylamino group.
Claims29
A compound comprising a plurality of linked nucleosides, wherein:
- each nucleoside includes a pentofuranosyl sugar portion and a base portion;
- and
- at least one of said nucleosides bears at a 2′-O-position, a 3′-O-position, or a 5′-O-position of said pentofuranosyl sugar a terminal substituent having formula:
- —RA—N(R1a)(R1b)
- where:
- RA is alkyl having from 1 to about 10 carbon atoms or (CH2—CH2—Q)x;
- R1a and R1b, independently, are H, R2, or an amine protecting group or have formula C(X)—R2, C(X)—RA—R2, C(X)—Q—RA—R2, C(X)—Q—R2;
- and
- R2 is a folate, a steroid molecule, a reporter molecule, a lipophilic molecule, a reporter enzyme, a peptide, a protein, or has formula —Q—(CH2CH2—Q—)x—R3;
- X is O or S;
- each Q is, independently, is NH, O, or S;
- x is about 1 to about 50;
- R3 is H, RA, C(O)OH, C(O)ORA, C(O)R4, RA—N3, or RA—NH2;
- R4 is Cl, Br, I, SO2R5 or has structure:
- m is 2 to 7;
- and
- R5 alkyl having 1 to about 10 carbon atoms.
A nucleoside comprising a pentofuranosyl sugar portion and a base portion, wherein said nucleoside bears at a 2′-O-position of said pentofuranosyl sugar, a 3′-O-position, or a 5′-O-position a substituent having the formula:
- —RA—N(R1a)(R1b)
- where:
- RA is alkyl having from 1 to about 10 carbon atoms;
- R1a and R1b, independently, are H, R2, or an amine protecting group or have formula C(X)—R2, C(X)—RA—R2, C(X)—Q—RA—R2, C(X)—Q—R2;
- and
- R2 is a steroid molecule, a reporter molecule, a lipophilic molecule, a reporter enzyme, a peptide, a protein, or has formula —Q—(CH2CH2—Q—)x—R3;
- X is O or S;
- each Q is, independently, is NH, O, or S;
- x is about 1 to about 50;
- R3 is H, RA, C(O)OH, C(O)ORA, C(O)R4, RA—N3, or RA—NH2;
- and
- R4 is Cl, Br, I, SO2R5 or has structure:
- m is 2 to 7;
- and
- R5 alkyl having 1 to about 10 carbon atoms.
Dependencies are inferred from the claim text.