Synthesis of oligonucleotides
AssigneeIsis Pharmaceuticals, Inc.
InventorsVasulinga Ravikumar, Douglas L. Cole
Life of this patent
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Abstract
Synthetic processes are provided for the solution phase synthesis of oligonucleotides, especially phosphorothioate oligonucleotides, and intermediate compounds useful in the processes. Intermediates having structure (I) are prepared in accordance with preferred embodiments.
Claims7
A method for the preparation of a plurality of target olgonucleotides having a plurality of common subsequences, comprising the steps of:
- analyzing the target oligonucleotides to identify the common subsequences;
- preparing oligonucleotide blocks having the common subsequences;
- phospitylating the oligonucleotides blocks;
- and
- performing solid phase synthesis to form the target oligonucleotides;
- wherein the synthons used in the solid phase synthesis comprise the phosphitylated ollgonucleotide blocks.
A method for the preparation of a plurality of target oligonucleotides, each of said target oligonucleotides comprising at least one common nucleotide subsequence, comprising:
- identifying said common nucleotide subsequences;
- providing an oligonucleotide synthon of formula:
- wherein:
- each Q is O;
- each Bx is independently a nucleosidic base;
- each X is independently, H, OH, F, O-alkyl or substituted O-alkyl wherein said substitution is amino, alkoxy or nitrogen heterocycle;
- each Z is independently O or S;
- Y is H or a hydroxyl protecting group;
- U is a phosphite activating group;
- each T is independently a phosphorous blocking group;
- and
- n is an integer from 1 to 200;
- said oligonucleotide synthon having one of said common nucleotide subsequences;
- and
- reacting said synthon with nucleoside precursors to form said plurality of target oligonucleotide.
A method for the preparation of a plurality of target oligonucleotides, each of said target oligonucleotides comprising more than one common nucleotide subsequence, comprising:
- identifying said common nucleotide subsequences;
- providing a plurality of oligonucleotide synthons of formula:
- wherein:
- each Q is O;
- each Bx is independently a nucleosidic base;
- each X is independently, H, OH, F, O-alkyl or substituted O-alkyl wherein said substitution is amino, alkoxy or nitrogen heterocycle;
- each Z is independently O or S;
- Y is H or a hydroxyl protecting group;
- U is a phosphite activating group;
- each T is independently a phosphorous blocking group;
- and
- n is an integer from 1 to 200 and
- wherein each of said oligonucleotide synthons has one of said common nucleotide subsequences;
- and
- reacting said plurality of oligonucleotide synthons with nucleoside precursors to form said plurality of target oligonucleotides.
Dependencies are inferred from the claim text.