Urocortin 2 analogs and uses thereof

Abstract

Disclosed are polypeptides that are analogs of urocortin 2 that have pharmacological activity similar to urocortin 2 but have improved water solubility compared to urocortin 2, and pharmaceutical compositions of the polypeptides of the present invention. Also disclosed are polynucleotides encoding the polypeptides, and methods of treating pathophysiological states employing pharmaceutical compositions of the polypeptides and polynucleotides of the present invention. In addition, disclosed are vectors and host cells that include a nucleic acid encoding a polypeptide of the present invention, and kits that include pharmaceutical compositions of the present invention.

1 - 36 . (canceled) 
     
     
         37 . A Urocortin 2 polypeptide or peptide derived from Urocortin 2, or a polypeptide variant thereof. 
     
     
         38 . A Urocortin 2 polypeptide or peptide derived from a prohormone of Urocortin 2 or a polypeptide variant thereof. 
     
     
         39 . The polypeptide or peptide of  claim 37  or  38 , wherein the C-terminus is amidated. 
     
     
         40 . The polypeptide or peptide of  claim 37 , wherein the polypeptide or peptide is modified. 
     
     
         41 . The polypeptide or peptide of  claim 40 , wherein the modification is the addition of a fatty acid or the addition of at least one amino acid residue. 
     
     
         42 . The polypeptide or peptide of  claim 37 , wherein the variant is a substitutional or an insertional mutant, wherein an insertional mutant contains one or more additional amino acid residues. 
     
     
         43 . The polypeptide or peptide of  claim 38 , wherein the variant is a substitutional or an insertional mutant, wherein an insertional mutant contains one or more additional amino acid residues. 
     
     
         44 . The polypeptide or peptide of  claim 39 , wherein the variant is a substitutional or an insertional mutant, wherein an insertional mutant contains one or more additional amino acid residues. 
     
     
         45 . The polypeptide or peptide of  claim 44 , wherein the at least one amino acid residue is selected from R and K or a combination thereof. 
     
     
         46 . The polypeptide or peptide of  claim 37 , wherein the N-terminus is modified by acylation or methylation. 
     
     
         47 . The polypeptide or peptide of  claim 37  or salts thereof. 
     
     
         48 . The polypeptide or peptide of  claim 37 , wherein the Urocortin 2 is SEQ ID NO: 1 or SEQ ID NO: 10. 
     
     
         49 . The polypeptide or peptide of  claim 37  or  38 , wherein the polypeptide or peptide is selected from the group consisting of SEQ ID NOS: 1-19 and 21-22. 
     
     
         50 . The polypeptide or peptide of  claim 37 , wherein the variant is a chimeric protein, a fusion protein or a chemical derivative. 
     
     
         51 . A composition comprising the polypeptide or peptide of  claim 37  in a pharmaceutically acceptable carrier. 
     
     
         52 . The composition of  claim 51 , wherein the pharmaceutical form is formulated for parenteral administration, for oral administration, or for injection via the intravenous, intramuscular, subcutaneous, or intraperitoneal routes. 
     
     
         53 . A method of treating congestive heart failure, low levels of ACTH secretion or abnormalities of glucose metabolism comprising administering to a subject a composition of  claim 49 . 
     
     
         54 . The method of  claim 53 , wherein the abnormalities of glucose metabolism are selected from the group consisting of diabetes, impaired glucose tolerance, and hyperglycemia.