Oligosaccharides comprising an aminooxy group and conjugates thereof

Abstract

The invention provides methods for the synthesis of oligosaccharides comprising an aminooxy group. The invention further provides oligosaccharides comprising an aminooxy group, methods for coupling oligosaccharides comprising an aminooxy group to glycoproteins, and oligosaccharide-protein conjugates. Also provided are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-protein conjugate.

1 - 55 . (canceled) 
     
     
         56 . A method of coupling an oligosaccharide to a protein, comprising:
 (a) providing an oligosaccharide comprising an aminooxy group;   (b) providing a protein having at least one carbonyl group; and   (c) reacting the aminooxy group of the oligosaccharide with the at least one carbonyl group of the protein,   thereby coupling the oligosaccharide to the protein, wherein the oligosaccharide comprising an aminooxy group is   
       
         
           
           
               
               
           
         
       
       wherein m is an integer from 1 to 10, and p is an integer from 1 to 10. 
     
     
         57 . The method of  claim 56 , wherein the protein is a glycoprotein and the at least one carbonyl group is obtained by oxidation of the glycoprotein with periodate. 
     
     
         58 . The method of  claim 56 , wherein the protein is a lysosomal enzyme. 
     
     
         59 . The method of  claim 58 , wherein the lysosomal enzyme is acid α-glucosidase, α-galactosidase A, acid sphinogyelinase, or α-L-iduronidase. 
     
     
         60 . The method of  claim 58 , wherein the lysosomal enzyme is acid α-glucosidase. 
     
     
         61 . The method of  claim 56 , wherein m is 3. 
     
     
         62 . The method of  claim 56 , wherein p is 1. 
     
     
         63 . The method of  claim 56 , wherein m is 3 and p is 1. 
     
     
         64 . The method of  claim 63 , wherein the protein is acid α-glucosidase. 
     
     
         65 . An oligosaccharide-protein conjugate produced by the method of  claim 56 . 
     
     
         66 . A pharmaceutical composition comprising the oligosaccharide-protein conjugate of  claim 65  and an excipient.