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 - 25 . (canceled) 
     
     
         26 . A method of treating a pathophysiological state in a subject, comprising administering to the subject a pharmaceutical composition comprising;
 a) an isolated polypeptide of formula (I):
   X 1 -X 2 -X 3 -X 4 -X 5 -X 6   (I)
 
   wherein X 1  is either absent or a polypeptide having 1-200 residues;   X 2  is absent or 1-20 amino acid residues that are each individually selected from either arginine (R) or lysine (K);   X 3  is SEQ ID NO:1, SEQ ID NO:19, SEQ ID NO:21, or SEQ ID NO:22;   X 4  is either absent, G, GH, or GHC;   X 5  is absent or 1-20 amino acid residues that are each individually selected from either arginine (R) or lysine (K);   X 6  is either absent or a polypeptide having 1-200 residues;   provided that if X 3  is SEQ ID NO:1, X 4 , X 5  and X 6  are all absent, then X 2  is not absent;   further provided that if X 3  is SEQ ID NO:19, X 5  is absent, and X 6  is absent, then X 4  is G GH, or GHC; and   b) a pharmaceutically acceptable carrier.   
     
     
         27 . The method of  claim 26 , wherein the subject is a mammal. 
     
     
         28 . The method of  claim 27 , wherein the mammal is a human, a primate, a horse, a cow, a sheep, a pig, a dog, a cat, a rat, or a mouse. 
     
     
         29 . The method of  claim 28 , wherein the mammal is a human. 
     
     
         30 . The method of  claim 26 , wherein the pathophysiological state is selected from the group consisting of high body temperature, appetite dysfunction, congestive heart failure, stress, anxiety, and undesirably low levels of ACTH secretion. 
     
     
         31 - 36 . (canceled)