Isozyme-specific activators of protein kinase C methods and compositions
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorDaria Mochly-Rosen
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Abstract
Isozyme-specific agonists or activators of .epsilon.PKC are disclosed. The agonists include peptides corresponding to the region of .epsilon.PKC between about amino acids 85 and 92. Also disclosed are therapeutic methods employing such .epsilon.PKC-specific agonists to induce preconditioning and thereby reduce injury due to subsequent ischemia, as well as methods for screening test compounds for .epsilon.PKC-selective agonist properties.
Claims27
A peptide selected from the group consisting of SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, and SEQ ID NO:19.
A method of reducing ischemic injury to a cell exposed to hypoxia conditions, comprising
- introducing into said cell, prior to exposure to said hypoxic conditions, a pharmaceutically-effective amount of an isozyme-specific .epsilon.PKC peptide agonist,
- wherein said pharmaceutically-effective amount of said isozyme-specific .epsilon.PKC peptide agonist is effective to cause preconditioning, and said preconditioning is effective to reduce ischemic injury to said cell caused by subsequent exposure to ischemic conditions relative to the ischemic injury suffered by a cell that did not undergo preconditioning.
A method of identifying a compound effective to induce preconditioning in a cell, comprising
- contacting an .epsilon.PKC polypeptide containing a RACK binding site with an .epsilon.PKC agonist peptide in the presence and absence of a test compound for inducing preconditioning in a cell,
- measuring the binding between said .epsilon.PKC polypeptide and said .epsilon.PKC agonist peptide in the presence and absence of said test compound, and
- identifying said test compound as being effective to induce preconditioning if binding in the presence of the test compound is significantly decreased relative to binding in the absence of the test compound.
Dependencies are inferred from the claim text.