Use of acid scavengers for the synthesis of standard length and long-mer polymer 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 preparing an array of polymers comprising:
providing a solid substrate comprising a reactive group protected by an acid labile protective group;
coating the solid substrate with a film, the film comprising an photo acid generator and an acid scavenger;
activating the photo acid generator in selected regions of the substrate by selective application of light having a predetermined wavelength to provide an acid, wherein the reactive group having the protective group is to contacted to the acid in the presence of the scavenger such that the protective group is removed to provide an exposed reactive group, wherein a step of baking is not performed following activation of the photoacid generator;
contacting the exposed reactive group with a monomer, wherein the monomer is coupled to the exposed reactive group; and
repeating the steps of coating; activating, and contacting the exposed reactive group with a monomer to produce the array of polymers.
2. A method according to claim 1 , wherein said polymer is a nucleic acid.
3. A method according to claim 1 , wherein said polymer is a polypeptide.
4. A method according to claim 3 , wherein the polypeptide comprises amino acid residues selected from one or more of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, praline, serine, threonine, tryptophan, tyrosine and valine.
5. A method according to claim 3 , wherein the polypeptide is a peptide nucleic acid.
6. A method according to claim 5 , wherein the peptide nucleic acid repeat unit is represented by one of the following formulae:
wherein B represents a base.
7. A method according to claim 6 , wherein B is adenine, cytosine, guanine or thymine.
8. A method according to claim 1 , wherein the PAG is selected from the group consisting of an ionic photoacid generator and a non-ionic photoacid generator.
9. A method according to claim 8 , wherein the PAG is an ionic photoacid generator.
10. A method according to claim 9 , wherein the ionic photoacid generator is an onium salt.
11. A method according to claim 10 , wherein the onium salt is bis-(4-t-butyl phenyl)iodonium PF 6 − .
12. A method according to claim 8 , wherein the PAG is a non-ionic photoacid generator.
13. A method according to claim 12 , wherein the non-ionic photoacid generator is 2,6-dinitrobenzyl tosylate.
14. A method according to claim 1 , wherein the acid scavenger is an organic base.
15. A method according to claim 14 , wherein the organic base is selected from the group consisting of primary, secondary and tertiary amines.
16. A method according to claim 15 , wherein the amines are represented by the structure:
wherein R 1 , R 2 and R 3 are independently H, an alkyl group, an alkenyl group, an alkynyl group or an aryl group, or one or more of R 1 , R 2 and R 3
taken together with the nitrogen atom form a carbocyclic or heterocyclic ring.
17. A process according to claim 14 , wherein acid scavenger is an organic base selected from the group consisting of:
18. A method according to claim 1 , wherein the acid scavenger is a polymeric base.
19. A method according to claim 18 , wherein the acid scavenger is a polymeric base selected from the group consisting of polyvinylpyridone, polyvinylpyridine and polyvinylimidazole.
20. A method according to claim 1 , wherein the predetermined wavelength of light is 310 nm or higher.