Cleavable linker for peptide synthesis

Abstract

The present invention provides a new building block for peptide synthesis, which introduces a cleavage site that can be used to generate cleavable fragments subsequent to a peptide sequence.

1 . A building block comprising the structure:
                       wherein 2 < n < 24, m = 2 or 3,   A is an acid labile protective group, and   B is a tag or base labile protective group.   
     
     
         2 . The building block of  claim 1 , wherein A is selected from the group consisting of tert-Butyloxycarbonyl (“Boc”) or Fluorenylmethyloxycarbonyl (“Fmoc”). 
     
     
         3 . The building block of  claim 1 , wherein B is selected from the group consisting of Boc or Fmoc. 
     
     
         4 . The building block of  claim 1 , wherein A is Boc and B is Fmoc; or A is Fmoc and B is Boc. 
     
     
         5 . The building block of  claim 1 , wherein m is 2. 
     
     
         6 . The building block of  claim 1 , wherein m is 3. 
     
     
         7 . The building block of  claim 1 , wherein n is 4. 
     
     
         8 . The building block of  claim 1 , wherein the building block is 
       
         
           
           
               
               
           
         
       
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         9 . The building block of  claim 1 , wherein the building block is 
       
         
           
           
               
               
           
         
       
       . 
     
     
         10 . A compound comprising the structure:
                       wherein 2 < n < 24, m = 2 or 3,   X is a peptide or a solid support, and   Y is selected from the group consisting of a peptide, a functional group, a tag, a peptide including a functional group or a tag, PEG, or a group including PEG.   
     
     
         11 . The compound of  claim 10 , wherein the tag is selected from the group consisting of a solubility enhancing tag or an immobilization tag. 
     
     
         12 . The compound of  claim 10 , wherein Y is selected from the group consisting of poly-lysine, poly-arginine, poly-glutamic acid, and poly-aspartic acid. 
     
     
         13 . The compound of  claim 10 , wherein the functional group is selected from the group consisting of hydrazine, aminooxy, azide, alkynyl, alkenyl, aldehyde, pyrroloalanine, carboxy, and thiol. 
     
     
         14 . The compound of  claim 10 , wherein Y comprises a peptide having between 2 and 120 residues. 
     
     
         15 . The compound of  claim 10 , wherein X and Y both comprise peptides. 
     
     
         16 . The compound of  claim 15 , wherein m is 2 and n is 2 or 3. 
     
     
         17 . The compound of  claim 15 , wherein m is 3 and n is 2 or 3. 
     
     
         18 . The compound of  claim 10 , wherein n is 2. 
     
     
         19 . The compound of  claim 10 , wherein n is 3. 
     
     
         20 . The compound of  claim 10 , wherein Y comprises a tag and X comprises a peptide.