OLIGONUCLEOTIDE SYNTHESIS WITH INTERMITTENT AND POST SYNTHETIC OXIDATION

• US 20070255054A1
• Filed: 01/02/2007
• Published: 11/01/2007
• Est. Priority Date: 12/30/2005
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Kuimelis, Robert, Bury, Paul
• Application Number:
  US11/619,046
• Publication Number:
  US 20070255054A1
• Time in Patent Office: Days
• US Class Current: 536/25.310
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Process for fabricating an array of polymers on a solid support is provided having the steps of coupling a monomer with a reactive side masked by a protecting group to a growing polymer chain, optionally capping the monomer or monomer chains that have not reacted in a given cycle, deprotecting the product with a deprotecting agent, repeating the above steps on regions of the support as necessary to give polymers having a desired sequence and length and oxidizing the inter monomer linkage post-synthetically.

Claims

1. A process for fabricating an array of polymers on a solid support, comprising the steps of:

(a) coupling a monomer with a reactive site masked by a protecting group to a growing polymer chain;

(b) optionally capping the monomer or monomer chains that have not reacted in a giving cycle;

(c) deprotecting the product with a deprotecting agent;

(d) repeating steps (a)-(c) on regions of support as necessary to give a polymers having a desired sequence and length; and

(e) oxidizing the intermonomer linkages post-synthetically.

2. The process of claim 1 wherein said array of polymers comprises an array of nucleic acids.

3. The process of claim 1 wherein said array of polymers comprises an array of oligonucleotides.

4. The process of claim 1 wherein said polymer is a DNA oligonucleotide.

5. The process of claim 1 wherein said monomer is a nucleotide.

6. The process of claim 1, wherein the protective group is a photolabile group.

7. The process of claim 5 wherein said nucleotide is protected at its 5′

hydroxyl end with a photolabile protective group.

8. The process of claim 5 wherein said nucleotide is protected at its 3′

hydroxyl group with a photolabile protective group.

9. The process of claim 1 wherein said deprotecting step comprises photolysis.

10. The process of claim 5 wherein said nucleotide is selected from the group consisting of G, A, T and C.

11. The process of claim 10 wherein said nucleotide selected from the group consisting of G, A, T, and C is protected at its 5′

hydroxyl group with a photolabile protective group.

12. The process of claim 1, wherein said intermonomer linkage is selected from the group consisting of phosphite triester, thiophosphite triester, and dithiophosphite triester bonds.

13. The process of claim 1 wherein the capping step is performed prior to oxidation.

14. The process of claim 1 wherein said array of polymers comprises a polymer at least 50 monomers in length.

15. The process of claim 13 wherein said array of polymers comprises a polymer at least 60 monomers in length.

16. A process of claim 14 wherein said array of polymers comprises a polymer at least 70 nucleotides in length.

17. An array of polymers produced in accordance with claim 1 comprising a feature is on the order of 10-100 μ

m.

18. An array of polymers produced in accordance with claim 1 having a feature on the order of 1-10 μ

m.

19. An array of polymers produced in accordance with claim 1 having a feature on the order of 100 to 1000 nm.