N-aryl-carbamic acid ester-derived and valeric acid ester-derived cross-linkers and conjugates, and methods for their synthesis and use

Abstract

The present invention describes carbamic acid ester-derived and valeric acid ester-derived polyfunctional cross-linker molecules, and methods for their synthesis and use. The inclusion of polymeric moieties such as poly(alkylene oxide) in the cross-linkers of the present invention can provide advantageous solubility properties in aqueous environments. Such cross-linkers may be used to form conjugates for use in a variety of assay formats.

1 . A compound of the formula:  
     
       
         
         
             
             
         
       
     
     wherein X is (alkylene oxide) n ; 
 n is between about 40 to about 450; and  
 Y is C 1-10  alkylene straight or branched chain comprising from 0-4 backbone heteroatoms, optionally substituted with from 1 to 4 substituents independently selected from the group consisting of C 1-6  alkyl straight or branched chain, halogen, trihalomethyl, C 1-6  alkoxy, —NO 2 , —NH 2 , ═O, —OH, —CH 2 OH, —C(O)NH 2 , and a linkage to a polyalkylene oxide moiety.  
 
   
   
       2 . A compound according to  claim 1  wherein Y═—(CH 2 ) a C(O)(CH 2 ) b — wherein a=1-3 and b=0-3, generating the compound shown:  
     
       
         
         
             
             
         
       
     
   
   
       3 . A compound according to  claim 1 , wherein X is a copolymer of two or more units selected from the group consisting of methylene oxide, ethylene oxide, propylene oxide, isopropylene oxide, and butylene oxide.  
   
   
       4 . A compound according to  claim 1 , wherein X is a homopolymer of units selected from the group consisting of methylene oxide, ethylene oxide, propylene oxide, isopropylene oxide, and butylene oxide.  
   
   
       5 . A compound according to  claim 1  wherein Y═—(CH 2 ) 2 C(O)NH— generating the compound shown:  
     
       
         
         
             
             
         
       
     
   
   
       6 . A compound of  claim 1  wherein n is between 60 and 100.  
   
   
       7 . A compound of  claim 1  wherein n is between 70 and 90.  
   
   
       8 . A compound of  claim 1  wherein n is about 77.  
   
   
       9 . A composition comprising a plurality of compounds of  claim 1  wherein said plurality of compounds comprise an average number for n of between 60 and 100.  
   
   
       10 . A composition comprising a plurality of compounds of  claim 1  wherein said plurality of compounds comprise an average number for n of between 70 and 90.  
   
   
       11 . A composition comprising a plurality of compounds of  claim 1  wherein said plurality of compounds comprise an average number for n of about 77.  
   
   
       12 . A compound of  claim 5  wherein n is between 60 and 100.  
   
   
       13 . A compound of  claim 5  wherein n is between 70 and 90.  
   
   
       14 . A compound of  claim 5  wherein n is about 77.  
   
   
       15 . A composition comprising a plurality of compounds of  claim 5  wherein said plurality of compounds comprise an average number for n of between 60 and 100.  
   
   
       16 . A composition comprising a plurality of compounds of  claim 5  wherein said plurality of compounds comprise an average number for n of between 70 and 90.  
   
   
       17 . A composition comprising a plurality of compounds of  claim 5  wherein said plurality of compounds comprise an average number for n of about 77.