Enzymatic nucleic acid peptide conjugates
OwnerLeonid Beigelman, Alex Azhayev +2inventors
InventorsLeonid Beigelman, Alex Azhayev, Elena Azhayeva, Maxim Antopolsky
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Abstract
This invention features conjugates, compositions, methods of synthesis, and applications thereof, including galactose, galactosamine, N-acetyl galactosamine, PEG, phospholipid, and human serum albumin (HSA) derived conjugates of nucleosides, nucleotides, non-nucleosides, and nucleic acids including enzymatic nucleic acids, DNAzymes, allozymes, antisense, dsRNA, siRNA, triplex oligonucleotides, 2,5-A chimeras, decoys and aptamers.
Claims96
A compound having Formula I:
- 17
- wherein X is an enzymatic nucleic acid molecule;
- each V independently is a protein or peptide;
- each R1, R2, and R3 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10,
A compound having Formula II:
- 18
- wherein X is an enzymatic nucleic acid molecule;
- V is a protein or peptide;
- each R1, R2, R3 and R4 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10.
A method for the synthesis of a compound having Formula I:
- 19
- wherein X is an enzymatic nucleic acid molecule;
- each V independently is a protein or peptide;
- each R1, R2, and R3 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10, comprising:
- (a) introducing a compound having Formula III:
- 20
- wherein V and n are as defined in Formula I, to a compound having Formula IV:
- 21
- wherein X, R1, R2, R3, and n are as defined in Formula I, under conditions suitable for the formation of a compound having Formula I.
A method for the synthesis of a compound having Formula II:
- 22
- wherein X is an enzymatic nucleic acid molecule;
- V is a protein or peptide;
- each R1, R2, R3 and R4 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10, comprising:
- (a) introducing a compound having Formula V:
- 23
- wherein V and R4 are as defined in Formula II, to a compound having Formula IV:
- 24
- wherein X, R1, R2, R3, and n are as defined in Formula II, under conditions suitable for the formation of a compound having Formula II.
A compound having Formula I:
- 25
- wherein X is a dsRNA, ssRNA, decoy, triplex oligonucleotide, aptamer, or 2,5-A chimera;
- each V independently is a protein or peptide;
- each R1, R2, and R3 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10.
A compound having Formula II:
- 26
- wherein X is a dsRNA, ssRNA, decoy, triplex oligonucleotide, aptamer, or 2,5-A chimera;
- V is a protein or peptide;
- each R1, R2, R3 and R4 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10.
A method for the synthesis of a compound having Formula I:
- 27
- wherein X comprises a dsRNA, ssRNA, decoy, triplex oligonucleotide, aptamer, or 2,5-A chimera;
- each V independently comprises a protein or peptide;
- each R1, R2, and R3 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10, comprising:
- (a) introducing a compound having Formula III:
- 28
- wherein V and n are as defined in Formula I, to a compound having Formula IV:
- 29
- wherein X, R1, R2, R3, and n are as defined in Formula I, under conditions suitable for the formation of a compound having Formula I.
A method for the synthesis of a compound having Formula II:
- 30
- wherein X is a dsRNA, ssRNA, decoy, triplex oligonucleotide, aptamer, or 2,5-A chimera;
- V is a protein or peptide;
- each R1, R2, R3 and R4 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylcyano, S, S-alkyl, S-alkylcyano, N or substituted N;
- and each n is independently an integer from about 1 to about 10, comprising:
- (a) introducing a compound having Formula V:
- 31
- wherein V and R4 are as defined in Formula II, to a compound having Formula IV:
- 32
- wherein X, R1, R2, R3, and n are as defined in Formula II, under conditions suitable for the formation of a compound having Formula II.
Dependencies are inferred from the claim text.