Methods for use of proinsulin transferrin fusion proteins as prodrugs

Abstract

The present invention provides compositions useful as prodrugs and methods for making the same. The compositions include a fusion protein having a first delivery domain and a second protein precursor domain linked together via a linker sequence. The delivery domain is a protein capable of facilitating entry to target cells via the endocytotic pathway, such as transferrin. The protein precursor is a prohormone or a profactor, such as proinsulin. Methods of this invention include the steps of selecting a protein suitable as the delivery domain, constructing a vector to encode the fusion protein, and expressing the fusion protein in a suitable expression host. Also disclosed is a method for targeted delivery of prodrugs to livers and a method of reducing hepatic glucose production.

What is claimed is: 
     
         1 . A method for forming a fusion protein useful as a prodrug, comprising:
 selecting a protein useful as a delivery domain for a protein precursor;   constructing a vector encoding said delivery domain linked to said protein precursor via a suitable linker sequence; and   expressing said fusion protein in a suitable expression host.   
     
     
         2 . The method of  claim 1 , wherein said delivery domain is transferrin. 
     
     
         3 . The method of  claim 1 , wherein said protein precursor is proinsulin. 
     
     
         4 . The method of  claim 1 , wherein said linker sequence is leucine-glutamate dipeptide.