Peptide nucleic acid conjugates

Abstract

The disclosure is directed to conjugates, e.g. PNA conjugates, as well as methods of employing the conjugates for detecting one or more targets in a biological sample, e.g. a tissue sample.

1 . A peptide nucleic acid oligomer having the structure of Formula (IB): 
       
         
           
           
               
               
           
         
         wherein 
         T is a group having between 1 and 4 carbon atoms and optionally substituted with O, N, or S and having a terminal reactive moiety; 
         ‘Linker’ is a branched or unbranched, linear or cyclic, substituted or unsubstituted, saturated or unsaturated, group having between 2 and 80 carbon atoms, and optionally having one or more heteroatoms selected from O, N, or S; 
         ‘PNA’ is a peptide nucleic acid sequence; 
         X is selected from the group consisting of biotin, an enzyme, a chromogen, a fluorophore, a hapten, and a mass spectrometry tag; 
         Y is a branched or unbranched, linear or cyclic, substituted or unsubstituted, saturated or unsaturated group having between 1 and 12 carbon atoms and optionally having one or more O, N, or S heteroatoms; 
         m is 0 or an integer ranging from 1 to 6; and 
         z is 0 or 1. 
       
     
     
         2 . The peptide nucleic acid oligomer of  claim 1 , wherein m is 0, z is 0, and n is greater than 1. 
     
     
         3 . The peptide nucleic acid oligomer of  claim 2 , wherein n is an integer ranging from between 2 and 6. 
     
     
         4 . The peptide nucleic acid oligomer of  claim 1 , wherein ‘Linker’ comprises at least one PEG group. 
     
     
         5 . The peptide nucleic acid oligomer of  claim 1 , wherein ‘Linker’ comprises a cleavable moiety selected from the group consisting of a photocleavable group and a chemically cleavable group. 
     
     
         6 . A conjugate having the structure of any of Formulas (I) or (II): 
       
         
           
           
               
               
           
         
         wherein 
         ‘Specific binding entity’ is selected from the group consisting of an antibody, an antibody fragment, a drug/antibody complex, and a nucleic acid; 
         ‘Linker’ is a branched or unbranched, linear or cyclic, substituted or unsubstituted, saturated or unsaturated, group having between 2 and 80 carbon atoms, and optionally having one or more heteroatoms selected from O, N, or S; 
         Z is selected from the group consisting of a peptide nucleic acid sequence, an uncharged DNA sequence, and a DNA sequence comprising charged and uncharged bases; 
         X is selected from the group consisting of biotin, an enzyme, a chromogen, a fluorophore, a hapten, and a mass spectrometry tag; 
         Y is a branched or unbranched, linear or cyclic, substituted or unsubstituted, saturated or unsaturated group having between 1 and 12 carbon atoms and optionally having one or more O, N, or S heteroatoms; 
         m is 0 or an integer ranging from 1 to 6; 
         z is 0 or 1; and 
         n is an integer ranging from 1 to 12. 
       
     
     
         7 . The conjugate of  claim 6 , wherein Z comprises a DNA sequence comprising only uncharged DNA bases. 
     
     
         8 . The conjugate of  claim 6 , wherein Z comprises a DNA sequence comprising a mixture of charged and uncharged bases. 
     
     
         9 . The conjugate of  claim 6 , wherein the ‘Specific Binding Entity’ is a primary antibody. 
     
     
         10 . The conjugate of  claim 6 , wherein Z is a peptide nucleic acid sequence comprising between about 5 and about 30 bases. 
     
     
         11 . The conjugate of  claim 6 , wherein Z is a peptide nucleic acid sequence comprising about 10 bases.