Addressable protein arrays

Abstract

Disclosed herein are arrays of nucleic acid-protein fusions which are immobilized to a solid surface through capture probes which include a non-nucleosidic spacer group and an oligonucleotide sequence to which the fusion (such as an RNA-protein fusion) is bound. Also disclosed herein are solid supports on which these arrays are immobilized as well as methods for their preparation and use (for example, for screening for protein-compound interactions such as protein-therapeutic compound interactions).

What is claimed is:  
     
         1 . A solid support having a linker layer on its surface, said linker layer being linked to an array of immobilized capture probes, each of said capture probes comprising a non-nucleosidic spacer group located proximal to the linker layer and an oligonucleotide sequence located distal to the linker layer, wherein said oligonucleotide sequence is bound to a nucleic acid-protein fusion.  
     
     
         2 . The solid support of  claim 1 , wherein said nucleic acid-protein fusion is an RNA-protein fusion.  
     
     
         3 . The solid support of  claim 1 , wherein said oligonucleotide sequence is bound to said nucleic acid-protein fusion by base pairing.  
     
     
         4 . The solid support of  claim 1 , wherein the protein is encoded by the nucleic acid.  
     
     
         5 . The solid support of  claim 1 , wherein said spacer group comprises polyalkylene oxide.  
     
     
         6 . The solid support of  claim 1 , wherein said spacer group comprises polyethylene oxide.  
     
     
         7 . The solid support of  claim 1 , wherein said spacer group comprises hexaethylene oxide.  
     
     
         8 . The solid support of  claim 1 , wherein said capture probe comprises a photocleavable linker.  
     
     
         9 . The solid support of  claim 1 , wherein said oligonucleotide sequence comprises a modified base.  
     
     
         10 . The solid support of  claim 9 , wherein said modified base is 5-propyne pyrimidine.  
     
     
         11 . The solid support of  claim 1 , wherein said oligonucleotide sequence comprises an internucleotide analog.  
     
     
         12 . The solid support of  claim 11 , wherein said internucleotide analog is a 3′-phosphoramidate linkage.  
     
     
         13 . The solid support of  claim 1 , wherein said oligonucleotide sequence comprises a carbohydrate modification.  
     
     
         14 . The solid support of  claim 13 , wherein said carbohydrate modification is a 2′-O-methyl group.  
     
     
         15 . The solid support of  claim 1 , wherein said nucleic acid-protein fusion comprises a hybridization tag sequence.  
     
     
         16 . The solid support of  claim 15 , wherein said hybridization tag sequence comprises a modified base.  
     
     
         17 . The solid support of  claim 15 , wherein said hybridization tag sequence comprises an intemucleotide analog.  
     
     
         18 . The solid support of  claim 1 , wherein each of said capture probes further comprises a reactive moiety.  
     
     
         19 . The solid support of  claim 18 , wherein said reactive moiety is a primary amino group.  
     
     
         20 . The solid support of  claim 1 , wherein said solid support is a glass or silica-based chip.  
     
     
         21 . The solid support of  claim 1 , wherein said nucleic acid-protein fusion is covalently linked to said capture probe.  
     
     
         22 . The solid support of  claim 21 , wherein said capture probe comprises one or more psoralen moieties.  
     
     
         23 . A solid support having a linker layer on its surface, said linker layer being linked to an array of immobilized capture probes, wherein each of said capture probes is attached to the linker layer of said solid support through a non-nucleosidic spacer group, and wherein each of said capture probes comprises an oligonucleotide sequence to which a nucleic acid-protein fusion is bound.  
     
     
         24 . The solid support of  claim 23 , wherein said nucleic acid-protein fusion is an RNA-protein fusion.  
     
     
         25 . A solid support comprising an array of immobilized capture probes, each of said capture probes comprising a non-nucleosidic spacer group and an oligonucleotide sequence to which a ribosome display particle is bound.  
     
     
         26 . A method for preparing a solid support, said method comprising the steps of: 
 (a) preparing a capture probe by linking a spacer group to an oligonucleotide sequence;    (b) attaching said capture probe to said solid support; and    (c) binding a nucleic acid-protein fusion to said capture probe.    
     
     
         27 . The method of  claim 26 , wherein said nucleic acid-protein fusion is an RNA-protein fusion.  
     
     
         28 . A method for preparing a solid support, said method comprising the steps of: 
 (a) attaching a spacer group to a surface of said solid support;    (b) attaching a bifunctional linker to said spacer group;    (c) attaching a capture probe to said bifunctional linker; and    (d) binding a nucleic acid-protein fusion to said capture probe.    
     
     
         29 . The method of  claim 28 , wherein said nucleic acid-protein fusion is an RNA-protein fusion.