Helix-grafted proteins as inhibitors of disease-relevant protein-protein interactions

Abstract

The disclosure provides helix grafted proteins, methods of producing helix grafted proteins and methods of use of helix grafted proteins as inhibitors of protein-protein interactions involved in disease pathogenesis.

What is claimed is: 
     
         1 . A method of inhibiting entry of virus into cells of a subject, the method comprising administering to the subject a composition comprising a helix grafted protein comprising at least 10 amino acids from a C-peptide from a virus grafted onto the solvent exposed α-helix of a protein selected from the group consisting of GLUE and ELMO, and wherein 1-20 solvent exposed amino acid residues in the α-helix are mutated. 
     
     
         2 . The method of  claim 1 , wherein the protein is ELMO. 
     
     
         3 . The method of  claim 1 , wherein the protein is GLUE. 
     
     
         4 . The method of  claim 1 , wherein the C-peptide comprises all or a portion of a gp41 C-peptide. 
     
     
         5 . The method of  claim 4 , wherein the gp41 C-peptide comprises at least 10 amino acids SEQ ID NO:2 (WMEWDREINNYTSLIHSLIEESQNQQEKNEQELL). 
     
     
         6 . The method of  claim 1 , wherein the protein is GLUE and the sequence of the extended grafted helix comprises SEQ ID NO:3 (GVWFSWATEIALYTILIHSLIEESQNQQEKNEQELL). 
     
     
         7 . The method of  claim 1 , wherein the protein is ELMO and the sequence of the extended grafted helix comprises SEQ ID NO:7 (WMEWDREINNYTSLIHSLIEESQNQQKQQRLNRLVE). 
     
     
         8 . The method of  claim 1 , wherein the protein is ELMO and the sequence of the extended grafted helix comprises SEQ ID NO:8 (DKWEYWIWTIGLYTLLGKSLIEESQNQQEKNEQELL). 
     
     
         9 . The method of  claim 1 , wherein the protein is ELMO and wherein the helix of ELMO is truncated. 
     
     
         10 . The method of  claim 1 , wherein the protein is ELMO and the C-peptide comprises residues 116 to 161 of SEQ ID NO:4. 
     
     
         11 . The method of  claim 1 , wherein the protein is ELMO and the sequence of the extended grafted helix comprises SEQ ID NO:8 (DKWEYWIWTIGLYTLLGKSLIEESQNQQEKNEQELL) and residues 150 to 161 of SEQ ID NO:4.