Methods of use of epsilon inhibitor compounds for the attenuation of pain

Abstract

The disclosure herein relates to modified εPKC inhibitory peptides, methods of generating such peptides, and method for using εPKC inhibitory peptides for the treatment of pain.

1 . A method of treating a subject suffering from pain, comprising:
 administering to the subject an effective amount of a hybrid construct comprising an epsilon protein kinase C (εPKC) inhibitory peptide, a gamma PKC (γPKC) inhibitory peptide and a carrier peptide, wherein the εPKC inhibitory peptide is covalently linked to the γPKC inhibitory peptide.   
     
     
         2 . The method of  claim 1 , wherein the pain is selected from the group consisting of acute pain, chronic pain, neuropathic pain, and inflammatory pain. 
     
     
         3 . The method of  claim 1 , wherein the pain is chronic pain. 
     
     
         4 . The method of  claim 1 , wherein at least one of the carrier peptide, the εPKC inhibitory peptide and the γPKC inhibitory peptide is modified at the C-terminus. 
     
     
         5 . The method of  claim 1 , wherein the carrier peptide comprises the amino acid sequence of SEQ ID NO:59. 
     
     
         6 . The method of  claim 1 , wherein the carrier peptide comprises the amino acid sequence of SEQ ID NO:4. 
     
     
         7 . The method of  claim 1 , wherein the carrier peptide is modified at its N-terminal end by an acyl, alkyl or sulfonyl group. 
     
     
         8 . The method of  claim 7 , wherein the carrier peptide is modified at its C-terminal end. 
     
     
         9 . The method of  claim 8 , wherein the modification at the N-terminal end of the carrier peptide is the formation of an amide. 
     
     
         10 . The method of  claim 1 , wherein the εPKC inhibitory peptide further comprises a terminal Cys. 
     
     
         11 . The method of  claim 10 , wherein the terminal Cys is located at the C-terminus of the εPKC peptide. 
     
     
         12 . The method of  claim 10 , wherein the terminal Cys is located at the N-terminus of the εPKC peptide. 
     
     
         13 . The method of  claim 1 , wherein the γPKC inhibitory peptide further comprises a terminal Cys. 
     
     
         14 . The method of  claim 13 , wherein the terminal Cys is located at the N-terminus of the γPKC inhibitory peptide. 
     
     
         15 . The method of  claim 13 , wherein the terminal Cys is located at the C-terminus of the γPKC inhibitory peptide. 
     
     
         16 . The method of  claim 10 , wherein the carrier peptide further comprises a terminal Cys. 
     
     
         17 . The method of  claim 16 , wherein the carrier peptide is linked to the εPKC inhibitory peptide via a disulfide bond. 
     
     
         18 . The method of  claim 13 , wherein the carrier peptide further comprises a terminal Cys. 
     
     
         19 . The method of  claim 18 , wherein the carrier peptide is linked to the γPKC inhibitory peptide via a disulfide bond.