Chemical amplification for the synthesis of patterned arrays

Abstract

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 - 51 . (canceled)  
     
     
         52 . A method for removing an acid labile protecting group from a synthesis intermediate comprising the steps of 
 a) forming a surface comprising a photosensitive active catalyst wherein said photosensitive active catalyst produces acid upon exposure to light of a pre-determined wavelength;    b) irradiating at least a part of said surface to remove said protecting group.    
     
     
         53 . A method recited in  claim 52  wherein said photosensitive compound is a PAC.  
     
     
         54 . A method recited in  claim 52  wherein said synthesis intermediate is a linker molecule.  
     
     
         55 . A method recited in  claim 52  wherein said synthesis intermediate is a DMT protected nucleotide.  
     
     
         56 . A method recited in  claim 52  wherein said synthesis intermediate is an oligonucleotide.  
     
     
         57 . A method recited in  claim 52  wherein said synthesis intermediate is an amino acid.  
     
     
         58 . A method recited in  claim 52  wherein said synthesis intermediate is an oligopeptide.  
     
     
         59 . A method for synthesizing an array of diverse polymers on a substrate comprising the steps of: 
 a) providing a substrate comprising a reactive functional group protected by an acid sensitive protecting group;    b) forming a surface on said substrate comprising a photosensitive active catalyst wherein said photosensitive active catalyst produces acid upon exposure to light of a pre-determined wavelength;    c) irradiating at least a part of said surface to remove said protecting group and expose said reactive functional group;    d) washing said substrate to remove said surface;    e) contacting said substrate with a synthesis intermediate to react with said exposed functional group; and    f) repeating steps a-e to form the desired array.    
     
     
         60 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 59  wherein said reactive functional group is selected from the group consisting of hydroxyl, amino, and carboxyl.  
     
     
         61 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 59  wherein said reactive functional group is a hydroxyl group.  
     
     
         62 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 61  wherein said hydroxyl groups are selected from the group consiting of a 5′ OH group of a ribonucleotide, 2′ deoxyribonucleotide, a 3′ OH group of a ribonucleotide and a 3′ OH group of a 2′ deoxyribonucleotide.  
     
     
         63 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 59  wherein said protecting group is DMT.  
     
     
         64 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 59  wherein said PAC is an onium salt.  
     
     
         65 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 59  wherein said surface additionally comprises a sensitizer.  
     
     
         66 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 59  wherein said synthesis intermediate is a monomer with a reactive functional group protected by an acid sensitive protective group.  
     
     
         67 . A method for synthesizing an array of diverse polymers on a substrate according to  claim 66  wherein said monomer is a nucleoside phosphoramidite.