Zwitterionic polymer bioconjugates and related methods

Abstract

Zwitterionic polymer and mixed charge copolymer bioconjugates, methods for making and using the bioconjugates.

1 . A mixed charge copolymer bioconjugate comprising one or more mixed charge copolymers covalently coupled to a biomolecule, wherein the mixed charge copolymer comprises a plurality of positively charged repeating units and a plurality of negatively charged repeating units, and wherein the mixed charge copolymer is substantially electronically neutral. 
     
     
         2 . The conjugate of  claim 1 , wherein the mixed charge copolymer comprises a plurality of repeating units and has the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 4  and R 5  are independently selected from hydrogen, fluorine, trifluoromethyl, C1-C6 alkyl, and C6-C12 aryl groups; 
         R 6 , R 7 , and R 8  are independently selected from hydrogen, alkyl, and aryl, and taken together with the nitrogen to which they are attached form a cationic center; 
         A(═O)—OM) is an anionic center, wherein A is C, SO, SO 2 , or PO, and M is a metal or organic counterion; 
         L 3  is a linker that covalently couples the cationic center [N + (R 6 )(R 7 )(R 8 )] to the polymer backbone; 
         L 4  is a linker that covalently couples the anionic center [A(═O)—OM] to the polymer backbone; 
         X −  is the counter ion associated with the cationic center; 
         n is an integer from 1 to about 10,000; and 
         p is an integer from 1 to about 10,000. 
       
     
     
         3 . The conjugate of  claim 1 , wherein R 4 -R 8  are independently selected from the group consisting of C1-C3 alkyl. 
     
     
         4 . The conjugate of  claim 1 , wherein L 3  is selected from the group consisting of —C(═O)O—(CH 2 ) n — and —C(═O)NH—(CH 2 ) n —, wherein n is 1-20. 
     
     
         5 . The conjugate of  claim 1 , wherein L 4  is —(CH 2 ) n —, where n is an integer from 1-20. 
     
     
         6 . The conjugate of  claim 1 , wherein the biomolecule is a protein, a nucleic acid, a carbohydrate, a lipid, a small molecule, or a small molecule agent. 
     
     
         7 . A composition, comprising the conjugate of  claim 1  and a pharmaceutically accepted carrier or diluent.