Process for the simultaneous synthesis of several oligonucleotides on a solid phase

• US 4,689,405 A
• Filed: 01/04/1984
• Issued: 08/25/1987
• Est. Priority Date: 01/20/1983
• Status: Expired due to Term

• Current Assignee: Gesellschaft Fur Biotechnologische Forschung mbH
• Original Assignee: Gesellschaft Fur Biotechnologische Forschung mbH
• Inventors: Heikens, Wiebke, Frank, Ronald
• Primary Examiner(s): Ore, Dale R.
• Application Number:
  US06/567,954
• Time in Patent Office: 1,329 Days
• Field of Search: 536/29, 536/27, 536/28
• US Class Current: 536/25.3
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof

Abstract

The present invention relates to a process for the simultaneous synthesis of several oligonucleotides on a solid phase by using supports of flat material. Finally, the present invention relates to an apparatus for carrying out said process.

Claims

1. A process for the simultaneous synthesis of a plurality of different oligonucleotides of predetermined nucleotide sequences on a solid phase, wherein the oligonucleotides are synthesized from mononucleotides, which comprises;

(a) providing from one to four groups of solid phase supports in the form of segments of flat material, each group of supports comprising at least one support, and the supports are linked to starting mononucleotide building blocks, which differ from group to group;

(b) providing from one to four reaction media, each containing a different mononucleotide building block;

(c) contacting the reaction media sequentially with the supports grouped in accordance with the predetermined sequences of the oligonucleotides

(d) where according to the method of synthesis chosen, a deprotection step may precede stage (c) above and a blocking step may follow stage (c) above.

2. A process according to claim 1, wherein there are used in stage (a) up to 4ⁿ groups of supports and oligomeric starting nucleotide building blocks that comprise 2 to n mononucleotides, n being an integer greater than 2.

4. A process according to claim 1, 2 or 3, wherein compounds selected from the group consisting of protected nucleosides, nucleotides or oligonucleotides are used as the building block.

5. A process according to claim 4, wherein a fibre-reinforced flat material based on material selected from the group consisting of cellulose, synthetic polymeric material or glass is used.

6. A process according to claim 5, wherein a flat material is used that is permeable to the liquid reaction medium and dissolved compounds contained therein.

3. A process for the simultaneous synthesis of a plurality of oligonucleotides of predetermined sequences on a solid phase, wherein oligonucleotides are built up from oligomeric nucleotide building blocks that comprise from 2 to n mononucleotides, n being an integer greater than 2, which comprises;

(a) providing groups of solid phase supports in the form of segments of flat material, each group of supports comprising at least one support, and the supports of each group are linked to starting nucleotide building blocks that differ from group to group;

(b) providing from one to 4ⁿ, reaction media, each containing a different oligomeric nucleotide building block

(c) contacting the reaction media sequentially with the supports that result from stage (a) above grouped in accordance with the predetermined sequences of the oligonucleotides

(d) where according to the method of synthesis chosen, a deprotection step may precede stage (c) above and a blocking step may follow stage (c) above and wherein there are one to n number of mononucleotides making up the starting nucleotide building blocks;

the number of groups of supports is up to 4ⁿ, the number of reaction media is up to 4ⁿ ; and

the number of mononucleotides making up the oligomeric nucleotide building blocks is from 2 to n;

n being a whole number greater than two.