Use of acid scavengers for the synthesis of standard length and long-mer nucleic acid arrays
View Patent ↗Protective groups which may be cleaved with an activatable deprotecting reagents are employed to achieve a highly sensitive, high resolution, combinatorial synthesis of pattern arrays of diverse polymers. In preferred embodiments of the instant invention, the activatable deprotecting reagent is a photoacid generator and the protective groups are DMT for nucleic acids and tBOC for amino acids. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.
1. A method for synthesizing an array of polymers, which comprises:
activating a photoacid generator (PAG) in selected regions of a substrate by directing a light to the selected regions, thereby producing an acid, wherein the substrate comprises a reactive group protected by an acid labile protecting group, and wherein the acid contacts the reactive group, thereby removing the acid labile protecting group;
contacting the substrate with a monomer; and
repeating the above steps, thereby synthesizing the array of polymers.
2. The method according to claim 1 , further comprising heating the substrate.
3. The method according to claim 1 , wherein the PAG is ionic or an onium salt.
4. The method according to claim 1 , wherein the PAG is selected from the group consisting of bis-(4-t-butyl phenyl)iodonium PF 6 − or 2,6-dinitrobenzyl tosylate.
5. The method according to claim 1 , further comprising including an acid scavenger in the activating step.
6. The method according to claim 1 , further comprising including a sensitizer during the activating step such that the sensitizer contacts the PAG.
7. The method according to claim 6 , wherein the acid is activated by the light at a longer wavelength than without the sensitizer.
8. The method according to claim 6 , further comprising coating the substrate with a film prior to the activating step, wherein the film comprises the PAG or the sensitizer.
9. The method according to claim 6 , wherein the sensitizer is an isopropyl thioxanthone.
10. The method according to claim 6 , wherein the sensitizer is selected from the group consisting of isopropylthioxanthone (ITX), 2-isopropyl thioxanthone, 2/4-isopropyl thioxanthone, and 10H-phenoxazine (PhX).
11. The method according to claim 7 , wherein the light is between 330 and 365 nm in wavelength.
12. The method according to claim 8 , wherein the film is a suspension.
13. The method according to claim 8 , wherein the film is poly(methyl methacrylate).
14. The method according to claim 5 , wherein the acid scavenger is an organic base.
15. The method according to claim 14 , wherein the acid scavenger has a boiling point above 150° C.
16. The method according to claim 14 , wherein the acid scavenger has a pKa between 8 and 10.
17. The method according to claim 14 , wherein the organic base has a sterically hindered nitrogen.
18. The method according to claim 14 , wherein the organic base is soluble in the film.
19. An array of polymers synthesized by a method which comprises:
activating a photoacid generator (PAG) in selected regions of a substrate by directing a light to the selected regions, thereby producing an acid, wherein the substrate comprises a reactive group protected by an acid labile protecting group, and wherein the acid contacts the reactive group, thereby removing the acid labile protecting group;
contacting the substrate with a monomer; and
repeating the above steps, thereby synthesizing the array of polymers.
20. The array of polymers synthesized by the method according to claim 19 , further comprising heating the substrate.
21. The array of polymers synthesized by the method according to claim 19 , further comprising including an acid scavenger in the activating step.
22. The array of polymers synthesized by the method according to claim 19 , further comprising including a sensitizer during the activating step such that the sensitizer contacts the PAG.
23. The array of polymers synthesized by the method according to claim 22 , wherein the acid is activated by the light at a longer wavelength than without the sensitizer.
24. The array of polymers synthesized by the method according to claim 22 , further comprising coating the substrate with a film prior to the activating step, wherein the film comprises the PAG or the sensitizer.
25. A method for synthesizing an array of polymers, which comprises:
activating a photoacid generator (PAG) in selected regions of a substrate by directing a light to the selected regions, thereby producing an acid, wherein the substrate comprises a hydroxyl group protected by an acid labile protecting group, and wherein the acid contacts the hydroxyl group, thereby removing the acid labile protecting group;
contacting the substrate with a monomer; and
repeating the above steps, thereby synthesizing the array of polymers.
26. The method according to claim 25 , wherein the hydroxyl group is selected from the group consisting of a hydroxyl group of a linker, a 5′ hydroxyl group of a nucleotide, and a 3′ hydroxyl group of a nucleotide.
27. The method according to claim 25 , further comprising coating the substrate with a film prior to the activating step, wherein the film comprises the PAG.
28. The method according to claim 27 , further comprising stripping the film from the substrate after the activating step.