Peptide kinase inhibitors and methods of use thereof

Abstract

Described herein are isolated regulatory peptides of protein kinase C, chimeric peptides thereof, and their variants. Use of the described peptides, in compositions and methods for treatment of cellular proliferation pathologies is also described.

1 . An isolated polypeptide comprising an amino acid sequence set forth as SEQ ID NO: 32. 
     
     
         2 . The isolated polypeptide of  claim 1 , wherein the amino acid at position 10 is alanine, as set forth herein as SEQ ID NO: 5. 
     
     
         3 . The isolated polypeptide of  claim 1 , wherein the amino acid at position 10 is cysteine, as set forth herein as SEQ ID NO: 1. 
     
     
         4 . An isolated polypeptide, comprising an amino acid sequence at least 70% identical to the sequence SEQ ID NOs: 1 or 5. 
     
     
         5 . An isolated polypeptide comprising an amino acid sequence at least 70% identical to the amino acid sequence set forth herein as SEQ ID NO: 11. 
     
     
         6 . The isolated polypeptide of  claim 1 , wherein the amino acid sequence comprises a myristoyl group. 
     
     
         7 . The isolated polypeptide of  claim 1 , further comprising at least one cell penetrating peptide (CPP). 
     
     
         8 . The isolated polypeptide of  claim 7 , wherein the CPP is penetratin. 
     
     
         9 . The isolated polypeptide of  claim 7 , wherein the amino acid sequence is the sequence set forth as SEQ ID NO: 2. 
     
     
         10 . The isolated polypeptide of  claim 1 , wherein the amino acid sequence is at least 70% identical to the amino acid sequence set forth as SEQ ID NO: 19. 
     
     
         11 . An isolated nucleic acid comprising a nucleic acid sequence encoding the isolated polypeptides of  claim 1 . 
     
     
         12 . An expression vector comprising the isolated nucleic acid of  claim 11 . 
     
     
         13 . A pharmaceutical composition comprising the isolated polypeptide of  claim 1  and a pharmaceutically-acceptable carrier or excipient. 
     
     
         14 .- 19 . (canceled) 
     
     
         20 . A method for treatment of a disease or condition associated with aberrant cell proliferation, comprising:
 administering to a subject in need thereof a therapeutically effective amount of the isolated peptide of  claim 1 , thereby treating the disease or condition.   
     
     
         21 . The method of  claim 20 , wherein the isolated peptide is provided to the subject as a nucleic acid capable of expressing the isolated peptide. 
     
     
         22 . The method of  claim 20 , wherein the disease or condition results in benign abnormal cell growth or a benign tumor. 
     
     
         23 . The method of  claim 20 , wherein the disease is a cancer. 
     
     
         24 . A method of inhibiting cell proliferation and/or cancer metastasis in a subject, comprising:
 administering to a subject in need thereof a therapeutically effective amount of the isolated peptide of  claim 1 , and optionally   administering to the subject a chemotherapeutic agent;   thereby inhibiting the cell proliferation and/or cancer metastasis.   
     
     
         25 . The method of  claim 24 , wherein the isolated peptide is provided to the subject as a nucleic acid capable of expressing the isolated peptide.