Activated Polyoxazolines and Conjugates and Compositions Comprising the Same

Abstract

The present disclosure provides POZ derivatives having a range of active functional groups allowing conjugation of POZ derivatives to a variety of target molecules under a wide range of reaction conditions to produce a hydrolytically stable target molecule-POZ conjugate. Furthermore, the present disclosure provides novel methods of synthesis for the disclosed POZ derivatives and hydrolytically stable target molecule-POZ conjugates created using the disclosed terminally activated monofunctional POZ derivatives. In one embodiment, the POZ derivative is a terminally activated monofunctional POZ derivative.

What is claimed: 
     
         1 . A hydrolytically stable target molecule-POZ conjugate of the general formula POZ-B-TM, wherein,
 POZ is a mono-functional POZ compound;   B is a hydrolytically stable linkage formed between the POZ compound and the target molecule; and   TM is a polypeptide target molecule.   
     
     
         2 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the mono-functional POZ compound is a POZ polymer having a single active functional group on a terminal end thereof, minus any leaving groups eliminated during the reaction of the active functional group on the POZ compound with a binding partner on TM. 
     
     
         3 . The hydrolytically stable target molecule-POZ conjugate of  claim 2 , wherein the POZ polymer has the structure R 1 -[N(COR 7 )CH 2 CH 2 ] n , wherein R 1  is hydrogen, an unsubstituted or substituted alkyl, alkenyl or aralkyl group and R 7  is independently selected for each repeating unit from an unsubstituted or substituted alkyl, alkenyl or aralkyl group and n is an integer from 3 to 1000. 
     
     
         4 . The hydrolytically stable target molecule-POZ conjugate of  claim 1  wherein the polypeptide contains an available amino group. 
     
     
         5 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the polypeptide contains an available thiol group. 
     
     
         6 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein B is an amide linkage. 
     
     
         7 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein B is a thioether linkage. 
     
     
         8 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein B is an amine linkage. 
     
     
         9 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the polypeptide is Dynorphin A 
     
     
         10 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the polypeptide is lysozyme. 
     
     
         11 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the polypeptide is insulin. 
     
     
         12 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the polypeptide is granulocyte macrophage colony stimulating factor. 
     
     
         13 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the polypeptide is apomyoglobin. 
     
     
         14 . The hydrolytically stable target molecule-POZ conjugate of  claim 1 , wherein the polypeptide is erythropoietin.