Compounds and methods for selective c-terminal labeling

Abstract

The present disclosure relates to compounds and methods for selective C-terminal functionalization of peptides. In certain embodiments, the compounds have improved water-solubility, and are suitable for use in connection with peptide sequencing methodologies.

1 - 110 . (canceled) 
     
     
         111 . A compound of Formula (XV): 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein
 P is a peptide; 
 Y 2  comprises a moiety resulting from a click reaction with an azide group; 
 L 5  is a linker or is absent; and 
 Z 2  comprises one or more of polyethylene glycol, single-stranded DNA, double-stranded DNA, biotin, and streptavidin. 
 
       
     
     
         112 . The compound or salt of  claim 111 , wherein Y 2  comprises a triazole. 
     
     
         113 . The compound or salt of  claim 111 , wherein L 5  is a linker. 
     
     
         114 . The compound or salt of  claim 113 , wherein the linker comprises a substituted or unsubstituted aliphatic chain, wherein one or more carbon atoms are optionally replaced by a heteroatom, an aryl, heteroaryl, cycloalkyl, or heterocyclyl moiety. 
     
     
         115 . The compound or salt of  claim 113 , wherein the linker comprises polyethylene glycol (PEG). 
     
     
         116 . The compound or salt of  claim 113 , wherein the linker comprises a peptide. 
     
     
         117 . The compound or salt of  claim 111 , wherein Z 2  comprises polyethene glycol. 
     
     
         118 . The compound or salt of  claim 111 , wherein Z 2  comprises single-stranded DNA. 
     
     
         119 . The compound or salt of  claim 111 , wherein Z 2  comprises double-stranded DNA. 
     
     
         120 . The compound or salt of  claim 111 , wherein Z 2  comprises biotin. 
     
     
         121 . The compound or salt of  claim 111 , wherein Z 2  comprises streptavidin. 
     
     
         122 . The compound or salt of  claim 111 , wherein P comprises 2-100 amino acid residues. 
     
     
         123 . The compound or salt of  claim 111 , wherein P comprises 2-30 amino acid residues. 
     
     
         124 . A surface, on which the compound or salt of  claim 111  is immobilized. 
     
     
         125 . The surface of  claim 124 , wherein the surface is a chip. 
     
     
         126 . A method of selective N-functionalization of a peptide, comprising reacting a plurality of peptides of Formula (XI): 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein each P independently is a peptide having an N-terminal amine, with a compound of Formula (XII): 
       
       
         
           
           
               
               
           
         
         under conditions comprising Cu 2+ , or a precursor thereof, and a buffer having a pH of 10-11; to obtain a plurality of ε-azido compounds of the Formula (XIIIb): 
       
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         127 . The method of  claim 126 , further comprising reacting the plurality of compounds of Formula (XIIIb), or a salt thereof, with a compound of Formula (XIV):
   R 6 -L 5 -Z 2    (XIV)
   wherein R 6  is a moiety comprising an alkyne or a strained alkene;
 L 5  is a linker or is absent; and 
 Z 2  comprises one or more of polyethylene glycol, single-stranded DNA, double-stranded DNA, biotin, and streptavidin; 
   to obtain a plurality of compounds of Formula (XV):   
       
         
           
           
               
               
           
         
         or a salt thereof, wherein Y 2  comprises a moiety resulting from a click reaction with the azide moiety of Formula (XIIIb), or a salt thereof, and R 6 .