Process for preparing polynucleotides
AssigneeUniversity Patents, Inc.
InventorsMarvin H. Caruthers, Mark D. Matteucci
Life of this patent
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Abstract
New and useful intermediate nucleotides bound to an inorganic polymer support, including the preparation thereof, and processes for the conversion to oligonucleotides which are especially useful for the synthesis of polynucleotides, particularly ribonucleic (RNA) and deoxyribonucleic acids (DNA).
Claims43
A modified inorganic polymer represented by the formula:
- ##STR5## wherein P is an inorganic polymer linked to the 3' or 5' --O-- of the nucleoside through a base hydrolyzable covalent bond;
- R is H or a blocking group;
- R.sub.1 is a hydrocarbyl radical containing up to 10 carbons;
- each B is a nucleoside or deoxynucleoside base;
- and each A is H or OR.
A modified inorganic polymer represented by the formula:
- ##STR6## wherein P is an inorganic polymer linked to the 3' --O through an ester linkage;
- R is H or a blocking group;
- R.sub.1 is a hydrocarbyl radical containing up to 10 carbons, each B is a nucleoside or deoxynucleoside base and each A is H or OR.
A modified inorganic polymer comprising an oligonucleotide or deoxyoligonucleotide covalently bound to said polymer through an ester linkage formed through the 3' --OH of the initial nucleoside moiety, wherein the terminal nucleoside is attached through a phosphite or phosphate triester linkage to the oligonucleotide chain and the 5' --O-- substituent is H or a blocking group.
A process for production of oligonucleotides which comprises the step of condensing the 3' --OH or 5' --OH group of a nucleoside or oligonucleotide covalently linked to an inorganic polymer by a coupling agent through the 5' --O-- or 3' --O--, respectively, of said nucleoside or oligonucleotide with a phosphite compound of the formula:
- ##STR7## wherein R is a blocking group;
- B is a nucleoside or deoxynucleoside base;
- A is H or OR;
- R.sub.1 is lower alkyl;
- and X is Cl or Br, or a secondary amino group.
A process for production of oligonucleotides which comprises the step of condensing a compound of the formula:
- ##STR9## wherein B is a nucleoside or deoxynucleoside base, A is H, OH or OR;
- and P is silica covalently bound to the nucleoside by the group --Z.sub.1 NHCOZCO-- wherein Z and Z.sub.1 are each alkylene of up to 5 carbon atoms, with a nucleoside phosphite compound of the formula:
- ##STR10## wherein A and B are as previously defined;
- R.sub.1 is lower alkyl;
- R is a blocking group;
- and X is Cl or Br, or a secondary amino.
A process for producing polynucleotides which comprises the step of condensing the 3' --OH or 5' --OH of a nucleoside linked to a functionalized inorganic polymer with a compound which is the reaction product of nucleoside and blocked phosphodichloridite.
Dependencies are inferred from the claim text.