The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective
receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing
consensus sequences with portions of
cytokine receptor ligands, including
Erythropoietin (EPO), that are not involved in the binding of the ligand to the
receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the
amino acid sequences of regions of
cytokine receptor ligands that are generally located on or within the region of the ligand
protein that is opposite of the
receptor complex, i.e., are generally derived from
amino acid sequences of regions of the ligand
protein that face away from the
receptor complex while the ligand is bound to the receptor. The invention is further directed to the
consensus sequences for use in
engineering a synthetic tissue protective
peptide. These tissue protective peptides also include fragments, chimeras, as well as peptides designed to mimic the
spatial localization of key
amino acid residues within the tissue protective receptor ligands, e.g., EPO. The invention further encompasses methods for treating or preventing a
disease or disorder using tissue protective peptides of the current invention. The invention also encompasses methods for enhancing excitable tissue function using tissue protective peptides of the current invention.