Methods of array synthesis
View Patent ↗Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. 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 and introducing latency into the synthesis of a polymer array, said polymer array selected from the group consisting of an oligonucleotide array and a peptide array, on a substrate comprising the steps of:
a) providing a surface having one or more synthesis intermediates bound thereon, said synthesis intermediates selected from the group consisting of a linker, a nucleotide, an amino acid, a peptide and an oligonucleotide, and the synthesis intermediates having a reactive group protected from reaction by a first photosensitive protecting group, said first protecting group having a first wavelength of light which removes said protecting group from said reactive group;
b) coating said surface with a substance comprising a photobleachable compound, wherein said photobleachable compound absorbs light having said first wavelength;
c) irradiating at least a part of said surface with light having said first wavelength to:
i) bleach said photobleachable compound; and
ii) remove said protective group;
d) removing said substance from said surface;
e) reacting a subsequently added synthesis intermediate, said subsequently added synthesis intermediate selected from the group consisting of a linker, a nucleotide an amino acid, a peptide and an oligonucleotide, with the unprotected reactive group, the subsequently added synthesis intermediate having a reactive group protected from reaction by a second photosensitive protecting group, wherein said first and second photosensitive protecting groups are the same or different and said protecting group having a second wavelength of light which removes said protecting group from said reactive group, wherein said first and said second wavelengths of light are the same or different;
f) recoating said surface with a substance comprising a photobleachable compound, wherein said photobleachable compound absorbs light having said second wavelength; if another synthesis intermediate is to be added; and
g) repeating steps b) through f) or not, until the desired polymer array is obtained.
2. The method of claim 1 wherein said synthesis intermediate is a nucleotide.
3. The method of claim 1 wherein said synthesis intermediate is a polynucleotide.
4. The methods of claim 1 wherein said synthesis intermediate is an amino acid.
5. The method of claim 1 wherein said photobleachable compound is a photobleachable dye.
6. The method of claim 5 wherein said photobleachable dye is pyrylium dye or diazomium dye.