Synthetic glycosulfopeptides and methods of synthesis thereof

Abstract

A new class of synthetic glycosulfopeptides (GSPs) which have one or more sulfated tyrosine residues and a glycan linked to the peptide, the glycan preferably including a sialyl Lewis x group or a sialyl Lewis a group. In a preferred version the GSPs have an O-glycan comprising a β1,6 linkage to a GalNAc. The present invention further contemplates in vitro methods of the synthesis of these GSPs without the use of the cells and methods of their use in vivo as powerful anti-inflammatory antithrombotic, or anti-metastatic compounds. The invention also contemplates a method of synthesizing oligosaccharides by cleaving the glycan from the GSP.

What is claimed is:  
     
         1 . A compound comprising the formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R is one of R 1 , R 3 -R 13  or R 15  of FIGS.  6 A- 6 C;  
 Tyr is a tyrosine residue;  
 SO 3   −  is a sulfate group;  
 C is an O-, N-, or S-linking amino acid residue; and  
 A, B and D are chains of from 0 to 12 amino acids each, with the proviso that the compound comprises no more than 38 amino acid residues.  
 
     
     
         2 . The compound of  claim 1  wherein A comprises one or two sulfated tyrosine residues.  
     
     
         3 . The compound of  claim 1  wherein C is serine, threonine, hydroxyproline, tyrosine, hydroxylysine, methionine, cysteine, arginine, lysine, glutamine, or asparagine.  
     
     
         4 . The compound of  claim 1  wherein R is R 1  of FIG. 6A.  
     
     
         5 . The compound of  claim 1  wherein R is R 3  of FIG. 6A.  
     
     
         6 . The compound of  claim 1  wherein R is R 4  of FIG. 6A.  
     
     
         7 . The compound of  claim 1  wherein R is R 5  of FIG. 6A.  
     
     
         8 . The compound of  claim 1  wherein R is R 6  of FIG. 6A.  
     
     
         9 . The compound of  claim 1  wherein R is R 7  of FIG. 6A.  
     
     
         10 . The compound of  claim 1  wherein R is R 8  of FIG. 6B.  
     
     
         11 . The compound of  claim 1  wherein R is R 9  of FIG. 6B.  
     
     
         12 . The compound of  claim 1  wherein R is R 10  of FIG. 6B.  
     
     
         13 . The compound of  claim 1  wherein R is R 11  of FIG. 6B.  
     
     
         14 . The compound of  claim 1  wherein R is R 12  of FIG. 6B.  
     
     
         15 . The compound of  claim 1  wherein R is R 13  of FIG. 6B.  
     
     
         16 . The compound of  claim 1  wherein R is R 15  of FIG. 6C.  
     
     
         17 . A composition comprising a therapeutically effective amount of the compound of  claim 1  and a pharmaceutically-acceptable carrier.  
     
     
         18 . A composition comprising a therapeutically effective amount of the compound of  claim 2  and a pharmaceutically-acceptable carrier.  
     
     
         19 . A composition comprising a therapeutically effective amount of the compound of  claim 3  and a pharmaceutically-acceptable carrier.  
     
     
         20 . A composition comprising a therapeutically effective amount of the compound of  claim 4  and a pharmaceutically-acceptable carrier.  
     
     
         21 . A composition comprising a therapeutically effective amount of the compound of  claim 5  and a pharmaceutically-acceptable carrier.  
     
     
         22 . A composition comprising a therapeutically effective amount of the compound of  claim 6  and a pharmaceutically-acceptable carrier.  
     
     
         23 . A composition comprising a therapeutically effective amount of the compound of  claim 7  and a pharmaceutically-acceptable carrier.  
     
     
         24 . A composition comprising a therapeutically effective amount of the compound of  claim 8  and a pharmaceutically-acceptable carrier.  
     
     
         25 . A composition comprising a therapeutically effective amount of the compound of  claim 9  and a pharmaceutically-acceptable carrier.  
     
     
         26 . A composition comprising a therapeutically effective amount of the compound of  claim 10  and a pharmaceutically-acceptable carrier.  
     
     
         27 . A composition comprising a therapeutically effective amount of the compound of  claim 11  and a pharmaceutically-acceptable carrier.  
     
     
         28 . A composition comprising a therapeutically effective amount of the compound of  claim 12  and a pharmaceutically-acceptable carrier.  
     
     
         29 . A composition comprising a therapeutically effective amount of the compound of  claim 13  and a pharmaceutically-acceptable carrier.  
     
     
         30 . A composition comprising a therapeutically effective amount of the compound of  claim 14  and a pharmaceutically-acceptable carrier.  
     
     
         31 . A composition comprising a therapeutically effective amount of the compound of  claim 15  and a pharmaceutically-acceptable carrier.  
     
     
         32 . A composition comprising a therapeutically effective amount of the compound of  claim 16  and a pharmaceutically-acceptable carrier.