Glycoconjugates and methods

Abstract

Disclosed are compositions containing glycoconjugates and methods for making the functionalized glycoconjugates, which include (a) contacting a cell with a first monosaccharide, and (b) incubating the cell under conditions whereby the cell (i) internalizes the first monosaccharide, (ii) biochemically processes the first monosaccharide into a second saccharide, (iii) conjugates the saccharide to a carrier to form a glycoconjugate, and (iv) extracellularly expresses the glycoconjugate to form an extracellular glycoconjugate comprising a selectively reactive functional group. Methods for forming products at a cell further comprise contacting the functional group of the extracellularly expressed glycoconjugate with an agent that selectively reacts with the functional group to form a product. Subject compositions include cyto-compatible monosaccharides comprising a nitrogen or ether linked functional group selectively reactive at a cell surface and compositions and cells comprising such saccharides.

1 - 6 . (canceled) 
     
     
         7 . A composition comprising a physiologically acceptable excipient and a cyto-compatible monosaccharide comprising a nitrogen or ether linked functional group selectively reactive at a cell surface, wherein the cytocompatible monosaccharide is of a formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein R 1  is a substituted or unsubstituted alkylene, alkenylene, alkynylene or arylene and R 2  is a substituted or unsubstituted alkyl, alkenyl, alkynyl or aryl wherein n is 2. 
       
     
     
         8 . The composition of  claim 7 , wherein the cyto-compatible monosaccharide is of the formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is alkylene, alkenylene, alkynylene or arylene; and wherein R 2  is an alkyl. 
       
     
     
         9 . The composition of  claim 8  wherein R 1  is —C 2 H 4 — and R 2  is —CH 3 . 
     
     
         10 . A composition comprising a physiologically acceptable excipient and a cyto-compatible monosaccharide comprising a nitrogen or ether linked functional group selectively reactive at a cell surface, wherein the cytocompatible monosaccharide is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein R 1  is a substituted or unsubstituted alkyl, alkenyl, alkynyl or aryl, R 2  is a substituted or unsubstituted alkylene, alkenylene, alkynylene or arylene and R 3  and R 4  are independently selected from O, S or are absent. 
       
     
     
         11 . The composition of  claim 10  wherein the compound is of formula (a), R 1  is —CH 3 , R 3  and R 4  are ═O, and R 2  is —C 2 H 4 —. 
     
     
         12 . The composition of  claim 10  wherein the compound is of formula (b), where R 2  is —CH 2  and R 3  is ═O. 
     
     
         13 . The composition of  claim 10  where R 2  is —CH 2  and R 3  is absent. 
     
     
         14 . The composition of  claim 13  where R 1  is —SH or —B(OH) 3 . 
     
     
         15 . The composition of  claim 7  further comprising the composition, of  claim 10 . 
     
     
         16 . (canceled) 
     
     
         17 . A method for engineering cell-surface epitopes for selective drug delivery comprising the step of contacting a cell with a composition of  claim 7  or  10 . 
     
     
         18 . The method of  claim 17  wherein the compound is selected from the group consisting of ManLev and FucLev. 
     
     
         19 . The method of  claim 17  further comprising the step of imaging the cell with a hydrazide-conjugated magnetic resonance imaging contrast agent. 
     
     
         20 . The method of  claim 17  further comprising the step of contacting the cell with ricin-hydrazide.