Small molecule printing

Abstract

The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm 2 . These compounds are typically attached to the solid support through a covalent interaction. In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.

What is claimed is: 
     
         1 . An array comprising a plurality of more than one type of chemical compound attached to a solid support through a linker of the formula: 
       
         
           
           
               
               
           
         
       
       wherein the density of the array of chemical compounds is at least 1000 spots per cm 2 . 
     
     
         2 . An array comprising a plurality of more than one type of chemical compound attached to a solid support, wherein the density of the array of chemical compounds is at least 1000 spots per cm 2 , and wherein the chemical compounds are attached to the solid support as shown below: 
       
         
           
           
               
               
           
         
       
       wherein:
 X is O, S, or NH of the attached chemical compound R; and 
 n is 0, 1, 2, 3, 4, or 5. 
 
     
     
         3 . The array of  claim 1 , wherein the array of chemical compounds is an array of small molecules. 
     
     
         4 . The array of  claim 1 , wherein the array of chemical compounds is an array of non-oligomeric chemical compounds. 
     
     
         5 . The array of  claim 1 , wherein the molecular weight of the chemical compounds is less than 1500 g/mol. 
     
     
         6 . The array of  claim 1 , wherein the density of the array of the chemical compounds is at least 5000 spots per cm 2 . 
     
     
         7 . The array of  claim 1 , wherein the solid support comprises a substantially flat surface. 
     
     
         8 . The array of  claim 1 , wherein the solid support is glass. 
     
     
         9 . The array of  claim 1 , wherein the solid support is derivatized glass. 
     
     
         10 . The array of  claim 1 , wherein the solid support is silylated glass. 
     
     
         11 . The array of  claim 1  wherein the solid support is γ-aminopropylsilylated glass. 
     
     
         12 . The array of  claim 1 , wherein the solid support is a polymer. 
     
     
         13 . The array of  claim 1 , wherein the solid support is metal. 
     
     
         14 . The array of  claim 1 , wherein the solid support is a metal-coated surface. 
     
     
         15 . The array of  claim 1 , wherein the attachment of the chemical compound to the solid support is characterized in that the attachment is robust enough so that the chemical compounds are (1) not inadvertently cleaved during subsequent manipulation steps and (2) inert so that the functionalities employed do not interfere with subsequent manipulation steps. 
     
     
         16 . The array of  claim 1 , wherein each of the chemical compounds becomes attached to the solid support through a reaction with an isothiocyanate moiety. 
     
     
         17 . A solid support comprising a solid support derivatized with isothiocyanate moieties. 
     
     
         18 . The solid support of  claim 17  comprising the structure: 
       
         
           
           
               
               
           
         
       
       wherein n is 0, 1, 2, 3, 4, or 5. 
     
     
         19 . A method for forming the array of  claim 1 , the method comprising:
 providing a solid support, wherein the solid support is derivatized with isothiocyanate moieties capable of interacting with more than one type of chemical compound to form a covalent linkage;   providing one or more solutions of the more than one type of chemical compound to be attached to the solid support; and   delivering the one or more solutions of the more than one type of chemical compound to the solid support, wherein each of the chemical compound is attached to the solid support through a covalent linkage, and wherein the density of the array of chemical compounds is at least 1000 spots per cm 2 .   
     
     
         20 . A method of identifying small molecule partners for biological macromolecules of interest, the method comprising:
 providing the array of  claim 1 , wherein the array comprises a plurality of more than one type of chemical compound, and wherein the density of the array of chemical compounds is at least 1000 spots per cm 2 ;   contacting the array with one or more types of biological macromolecules of interest; and   determining the binding of specific chemical compound-biological macromolecule partners.