Carbohydrate ligands that bind to igm antibodies against myelin-associated glycoprotein

Abstract

The invention relates to carbohydrate ligands presenting the minimal Human Natural Killer-1 (HNK-1) epitope that bind to anti-MAG (myelin-associated glycoprotein) IgM antibodies, and their use in diagnosis as well as for the treatment of anti-MAG neuropathy. In particular, the invention relates to disaccharides of formula (I) and (II) wherein Z is optionally substituted phenyl, heteroaryl, arylcarbonyl, or heteroarylmethyl, and to therapeutically acceptable polymers comprising a multitude of substituents of formula (I) and/or formula (II), wherein Z is a bifunctional linker connecting the disaccharides to the polymer backbone.

1 .- 16 . (canceled) 
     
     
         17 . A support comprising an immobilized compound of formula (I), or formula (II), or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein:
 Z is optionally substituted phenyl, heteroaryl, arylcarbonyl, or heteroarylmethyl; and 
 the compound is linked via Z to the support. 
 
       
     
     
         18 . The support of  claim 17 , wherein the support is a microtiter plate or a bead. 
     
     
         19 . The support of  claim 17 , wherein the support comprises a polymeric backbone. 
     
     
         20 . The support of  claim 17 , wherein Z comprises optionally substituted phenyl. 
     
     
         21 . The support of  claim 17 , wherein Z comprises phenyl substituted by alkylene with 3 to 25 carbon atoms. 
     
     
         22 . The support of  claim 21 , wherein one or more carbon atoms of the alkylene is replaced by nitrogen carrying a hydrogen atom, and one or more of the adjacent carbon atoms is substituted by oxo, representing an amide function —NH—CO—. 
     
     
         23 . The support of  claim 21 , wherein one or more of the carbon atoms of the alkylene is replaced by oxygen. 
     
     
         24 . The support of  claim 21 , wherein one or more of the carbon atoms of the alkylene is replaced by sulfur. 
     
     
         25 . The support of  claim 20 , wherein Z comprises 4-(2-aminoethyl)phenyl or 4-(2-(4-mercaptobutanoylamino)ethyl)phenyl linked to the support. 
     
     
         26 . The support of  claim 20 , wherein Z comprises substituted p-methoxyphenyl. 
     
     
         27 . The support of  claim 20 , wherein Z is of formula (I) 
     
     
         28 . The support of  claim 20 , wherein Z is of formula (II). 
     
     
         29 . A method of binding IgM autoantibodies against the Human Natural Killer-1 (HNK-1) epitope in a bodily fluid sample of a patient comprising:
 (i) providing a bodily fluid sample of a patient;   (ii) contacting the sample with a support according to  claim 17  to bind IgM autoantibodies against the HNK-1 epitope present in said bodily fluid sample; and   (iii) separating the contacted sample from the support.   
     
     
         30 . The method of  claim 29 , wherein the human bodily fluid is serum, plasma, blood or cerebrospinal fluid. 
     
     
         31 . The method of  claim 29 , wherein the method further comprises detecting the bound IgM autoantibodies on the support. 
     
     
         32 . The method of  claim 29 , wherein the patient is a human. 
     
     
         33 . A kit for binding IgM autoantibodies against the Human Natural Killer-1 (HNK-1) epitope in a bodily fluid sample of a patient comprising a support according to  claim 17 .