Compositions and methods for array-based genomic nucleic acid analysis of biological molecules

Abstract

The invention provides biological molecules modified by reaction with a compound having the formula: R 1 —X—R 2 , wherein R 1 is a cyclic ether group or an amino group, R 2 is an alkoxysilane group and X is a moiety chemically suitable for linking the cyclic ether group or the amino group to the alkoxysilane group. The invention also provides arrays, or “biochips,” comprising these modified biological molecules. Also provided are methods for making and using these compositions.

1 . A modified biological molecule comprising a biological molecule modified by reaction with a compound having the formula: R 1 —X—R 2 , wherein R 1  is a cyclic ether group or an amino group, R 2  is an alkoxysilane group and X is a moiety chemically suitable for linking the cyclic ether group or the amino group to the alkoxysilane group.  
     
     
         2 . The modified biological molecule of  claim 1 , wherein the cyclic ether is a compound comprising an epoxide group.  
     
     
         3 . The modified biological molecule of  claim 2 , wherein the epoxide is ethylene oxide.  
     
     
         4 . The modified biological molecule of  claim 1 , wherein the cyclic ether is an oxirane group.  
     
     
         5 . The modified biological molecule of  claim 1 , wherein the cyclic ether is a compound comprising an aromatic hydrocarbon epoxide group.  
     
     
         6 . The modified biological molecule of  claim 1 , wherein the R 1  group reacts with the biological molecule.  
     
     
         7 . The modified biological molecule of  claim 6 , wherein the R 1  group is covalently bound to the biological molecule.  
     
     
         8 . The modified biological molecule of  claim 1 , wherein the biological molecule comprises a polypeptide, a peptide or a peptidomimetic.  
     
     
         9 . The modified biological molecule of  claim 1 , wherein the biological molecule comprises a polysaccharide, or an analog or a mimetic thereof.  
     
     
         10 . The modified biological molecule of  claim 1 , wherein the biological molecule comprises a lipid, or an analog or a mimetic thereof.  
     
     
         11 . The modified biological molecule of  claim 1 , wherein the biological a molecule comprises a small molecule.  
     
     
         12 . The modified biological molecule of  claim 1 , wherein the biological molecule comprises a nucleic acid or an analog or mimetic thereof.  
     
     
         13 . The modified biological molecule of  claim 12 , wherein the nucleic acid comprises a DNA or an RNA.  
     
     
         14 . The modified biological molecule of  claim 12 , wherein the nucleic acid reacts with the R 1  group at its 5′ end.  
     
     
         15 . The modified biological molecule of  claim 12 , wherein the nucleic acid is an oligonucleotide.  
     
     
         16 . The modified biological molecule of  claim 12 , wherein the nucleic acid comprises a telomeric structure.  
     
     
         17 . The modified biological molecule of  claim 12 , wherein the nucleic acid comprises a chromatin structure.  
     
     
         18 . The modified biological molecule of  claim 1 , wherein cyclic ether is an epoxide group and the alkoxysilane is —Si(OCH 3 ) 3 , —Si(OC 2 H 5 ) 3 , —Si(OCH 3 )H 2 , —Si(OCH 3 )(CH 3 ) 2 , or —Si(OCH) 3 ) 2 CH 3 .  
     
     
         19 . The modified biological molecule of  claim 1 , wherein cyclic ether is an epoxide group and the compound is 3-glycidoxypropyltrimethoxysilane (GPTS).  
     
     
         20 . The modified biological molecule of  claim 1 , wherein the R 1  amino group comprises a primary amino group.  
     
     
         21 . The modified biological molecule of  claim 1 , wherein R 1  is an amino group and the alkoxysilane is selected from the group consisting of —Si(OCH 3 ) 3 , —Si(OC 2 H 5 ) 3  and  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2  and R 3  are selected from the group consisting of —H, —CH 3 , —OCH 3 , and —OC 2 H 3 , and provided that at least one of R 1 , R 2  or R 3  is either —OCH 3  or —OC 2 H 3 .  
     
     
         22 . The modified biological molecule of  claim 1  wherein R 1  is an amino group and the compound is 3-aminopropyltriethoxysilane.  
     
     
         23 - 81 . (canceled)  
     
     
         82 . A method for making a modified biological molecule comprising 
 (a) providing a biological molecule;    (b) providing a compound having the formula: R 1 —X—R 2  wherein R 1  is a cyclic ether group or an amino group, R 2  is an alkoxysilane group and X is a moiety chemically suitable for linking the cyclic ether group or the amino group to the alkoxysilane group; and    (c) reacting the biological molecule with the compound, thereby modifying the biological molecule with the compound.    
     
     
         83 . (canceled)  
     
     
         84 . The method of  claim 82  further comprising selecting the biological molecule from a polypeptide, a peptide or a peptidomimetic.  
     
     
         85 . The method of  claim 82  further comprising selecting the biological molecule from a polysaccharide, or an analog or a mimetic thereof.  
     
     
         86 . The method of  claim 82  further comprising selecting the biological molecule from a lipid, or an analog or a mimetic thereof.  
     
     
         87 . The method of  claim 82  further comprising selecting the biological molecule comprises a nucleic acid or an analog or mimetic thereof.