Process for preparing polynucleotides
AssigneeUniversity Patents, Inc.
InventorsMarvin H. Caruthers, Mark D. Matteucci
Life of this patent
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Abstract
This invention is a process for the production of oligonucleotides which comprises: (a) converting an inorganic polymer into a coupling agent-polymer; (b) combining the coupling agent-polymer with a blocked nucleoside to obtain a blocked nucleoside-modified support; and (c) removing the blocking group from the blocked nucleoside-modified support to provide for the coupling of nucleotides to the nucleoside-modified support.
Claims26
A process for the production of oligonucleotides which comprises:
- (a) converting an inorganic polymer into a coupling agent-polymer;
- (b) combining the coupling agent-polymer with a blocked nucleoside to obtain a blocked nucleoside-modified support;
- and
- (c) removing the blocking group from the blocked nucleoside-modified support to provide for the coupling of nucleotides to the nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) treating an inorganic polymer with a coupling agent which agent has a reactive group capable of reacting with a reactive group carried on a nucleoside;
- and
- (b) combining the treated polymer with a nucleoside or a blocked nucleoside to obtain a nucleoside-modified support or a blocked nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) providing an inorganic polymer;
- (b) converting the polymer into an amino-polymer;
- (c) providing a nucleoside
- (d) combining the amino-polymer and the nucleoside to obtain a nucleoside-modified support;
- and
- (e) attaching nucleotides to the nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) converting an inorganic silica into a coupling agent-silica,
- (b) combining the coupling agent-silica with a blocked nucleoside to obtain a blocked nucleoside-modified support;
- and
- (c) removing the blocking group from the blocked nucleoside-modified support to provide for the coupling of nucleotides to the nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) treating an inorganic silica with a coupling agent which agent has a reactive group capable of reacting with a reactive group carried on a nucleoside;
- and
- (b) combining the treated silica with a nucleoside or a blocked nucleoside to obtain a nucleoside-modified support or a blocked nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) providing an inorganic silica;
- (b) converting the silica gel into a coupling agent amino-silica;
- (c) providing a nucleoside;
- (d) combining the amino-silica and the nucleoside to obtain a nucleoside-modified support;
- and
- (e) attaching nucleotides to the nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) converting a silica gel into a coupling agent-silica gel;
- (b) combining the coupling agent-silica gel with a blocked nucleoside to obtain a blocked nucleoside-modified support;
- and
- (c) removing the blocking group from the blocked nucleoside-modified support to provide for the coupling of nucleotides to the nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) treating a silica gel with a coupling agent which agent has a reactive group capable of reacting with a reactive group carried on a nucleoside;
- (b) combining the treated silica gel with a nucleoside or a blocked nucleoside to obtain a nucleoside-modified support or a blocked nucleoside-modified support, and
- (c) attaching nucleotides to the nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) providing a silica gel;
- (b) converting the silica gel into a coupling agent amino-silica gel;
- (c) providing a nucleoside;
- (d) combining the amino-silica gel and the nucleoside to obtain a nucleoside-modified support;
- and
- (e) attaching nucleotides to the nucleoside-modified support.
A process for the production of oligonucleotides which comprises:
- (a) providing a silica gel support material;
- (b) converting said silica gel to a derivatize silica gel containing aminoalkyl or hydroxyalkyl groups;
- (c) providing a nucleoside modified to contain the half ester of a dicarboxylic acid;
- and
- (d) combining the nucleoside ester with the derivatized silica gel, to obtain a nucleoside modified silica gel support.
A process for the production of oligonucleotides which comprises:
- (a) providing a silica gel support material;
- (b) converting the silica gel to a derivatized silica gel containing aminoalkyl groups or hydroxyalkyl groups;
- (c) reacting the derivatized silica gel with a dicarboxylic acid to form an amine or ester linkage having carboxy functionality;
- and
- (d) condensing the free carboxy groups on the silica with a free hydroxy group of a nucleoside, to obtain a nucleoside modified silica gel support.
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:
- ##STR5## 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 formed by the removal of the hydrogen atom from a ring nitrogen of a nitrogen heterocyclic compound which contains unsaturated bonds in the ring structure.
A method of creating polynucleotides including the following steps:
- providing a resin support;
- providing an activated ester of a nucleoside;
- and
- combining the activated ester of the nucleoside and the resin support to obtain a resin-supported nucleoside.
In a method of producing a polynucleotide, the steps of:
- providing a resin-supported nucleoside;
- combining a monotrizolide and the resin-supported nucleoside in the presence of a nucleophilic catalyst to provide a dimethoxytrityl resin;
- and
- substituting the dimethoxytritly group in the dimethoxytrityl resin with a hydroxyl group to form the polynucleotide.
Dependencies are inferred from the claim text.