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 . In particularly preferred embodiments, these compounds are attached to the solid support through a covalent interaction. In general, these inventive arrays are generated by: (1) providing a solid support, wherein said solid support is functionalized with a selected chemical moiety capable of interacting with a desired chemical compound to form an attachment; (2) providing one or more solutions of one or more types of compounds to be attached to the solid support; and (3) delivering said one or more types of compounds to the solid support, whereby an array is formed and the array of compounds has a density of at least 1000 spots per cm 2 . In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest comprising: (1) providing an array of compounds, wherein the array has a density of at least 1000 spots per cm 2 ; (2) contacting the array with one of more types of biological macromolecules of interest; and (3) determining the interaction of specific small molecule-biological macromolecule partners.

1 - 18 . (canceled)  
     
     
         19 . A method for forming an array of more than one type of non-oligomeric compound attached to a solid support the method comprising: 
 providing a solid support, wherein said solid support is functionalized with a selected chemical moiety capable of interacting with more than one type of non-oligomeric chemical compound to form a covalent linkage;    providing one or more solutions of more than one type of non-oligomeric chemical compounds to be attached to the solid support; and    delivering said one or more solutions of said more than one type of chemical compounds to the solid support, whereby each of said chemical compounds is attached to the solid support through a covalent linkage, and whereby said array of compounds has a density of at least 1000 spots per cm 2 .    
     
     
         20 . The method of  claim 19 , wherein said solid support comprises a glass slide.  
     
     
         21 . The method of  claim 19 , wherein said chemical moiety comprises an electrophilic Michael acceptor.  
     
     
         22 . The method of  claim 19 , wherein said chemical moiety comprises a silyl halide.  
     
     
         23 . The method of  claim 22 , wherein said halide is selected from the group consisting of chloride, bromide, and iodide.  
     
     
         24 . The method of  claim 19 , wherein said chemical moiety comprises silyl tosylate.  
     
     
         25 . The method of  claim 19 , wherein said chemical moiety comprises silyl mesylate.  
     
     
         26 . The method of  claim 19 , wherein providing a solution of one or more types of compounds to be attached to the solid support comprises providing one or more solutions generated from a library of compounds, wherein each member of said library is initially attached to a bead, placed in an individual well, then cleaved from the bead to provide the solution.  
     
     
         27 . A method for forming an array of one or more types of non-oligomeric chemical compounds attached to a solid support, the method comprising: 
 providing a glass or polymeric solid support, wherein said solid support is functionalized with a selected chemical moiety capable of interacting with one or more types of non-oligomeric chemical compounds to form a covalent linkage;    providing one or more solutions of said one or more types of non-oligomeric compounds to be attached to the glass or polymer solid support; and    delivering said one or more solutions of said one or more types of non-oligomeric chemical compounds to the solid support, whereby each of said chemical compounds is attached to the solid support though a covalent linkages, and whereby said array of non-oligomeric compounds has a density of at least 1000 spots per cm 2 .    
     
     
         28 . The method of  claim 27 , wherein said chemical moiety comprises an electrophilic Michael acceptor.  
     
     
         29 . The method of  claim 27 , wherein said chemical moiety comprises a silyl halide.  
     
     
         30 . The method of  claim 29 , wherein said halide is selected from the group consisting of chloride, bromide, and iodide.  
     
     
         31 . The method of  claim 27 , wherein said chemical moiety comprises silyl tosylate.  
     
     
         32 . The method of  claim 27 , wherein said chemical moiety comprises silyl mesylate.  
     
     
         33 . The method of  claim 27 , wherein providing a solution of one or more types of compounds to be attached to the solid support comprises providing one or more solutions generated from a library of compounds, wherein each member of said library is initially attached to a bead, placed in an individual well, then cleaved from the bead to provide the solution.  
     
     
         34 . (canceled)  
     
     
         35 . (canceled)  
     
     
         36 . The method of  claim 19 , wherein the non-oligomeric chemical compounds are small molecules.  
     
     
         37 . The method of  claim 19 , wherein the non-oligomeric chemical compounds are non-peptidic and non-oligomeric chemical compounds.  
     
     
         38 . The method of  claim 19 , wherein the covalent linkage is characterized in that the linkage is robust enough so that the 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.  
     
     
         39 . The method of  claim 19 , wherein the array of compounds has a density of at least 5000 spots per cm 2 .  
     
     
         40 . The method of  claim 19 , wherein the array of compounds has a density of at least 10,000 spots per cm 2 . 
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