Isozyme-specific antagonists of protein kinase c

Abstract

A method of changing or otherwise converting the biological activity of a PKC peptide agonist to a peptide antagonist is described. The method involves substituting one or more amino acid residues so as to effect a change in charge in the peptide and/or to otherwise make the sequence similar to a sequence derived from the PKC binding site on the RACK protein for the respective PKC enzyme. Methods of inhibiting the activity of a PKC enzyme, and various peptide antagonists of εPKC are also disclosed.

1 . A composition consisting of a peptide with at least 70% sequence identity to SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7 said peptide attached by an N-terminal cysteine residue to a peptide to facilitate transport cellular uptake. 
     
     
         2 . The composition of  claim 1 , wherein the peptide to facilitate transport cellular uptake is selected from the group consisting of a Tat-derived peptide, an Antennapedia homeodomain-derived sequence, and a polyarginine peptide. 
     
     
         3 . The composition of  claim 2 , wherein the peptide to facilitate transport cellular uptake is selected from the group consisting of SEQ ID NO:91 and SEQ ID NO:92. 
     
     
         4 . A composition of  claim 2 , wherein said Tat-derived peptide has a sequence identified as SEQ ID NO:92. 
     
     
         5 . A treatment method, comprising administering to a patient in need thereof a therapeutically effective amount of a peptide having the amino acid sequence set forth in  claim 1 . 
     
     
         6 . The method of  claim 5 , wherein said administering is by a route selected from the group consisting of intravenous, parenteral, subcutaneous, inhalation, intranasal, sublingual, mucosal, and transdermal.