Ang (1-7) derviative oligopeptides for the treatment of pain

Abstract

The present invention provides oligopeptides, in particular, Ang-(1-7) derivatives, and methods for using and producing the same. In one particular embodiment, oligopeptides of the invention have higher blood-brain barrier penetration and/or in vivo half-life compared to the native Ang-(1-7), thereby allowing oligopeptides of the invention to be used in a wide variety of clinical applications including in treatment of cognitive dysfunction and pain.

What is claimed is: 
     
         1 . A method for treating a painful condition in a subject comprising administering a therapeutically effective amount of an oligopeptide having the formula: A 1 -A 2 -A 3 -A 4 -A 5 -A 6 -A 7 -A 8  (SEQ ID NO:1) wherein
 A 1  is selected from the group consisting of alanine and glutamic acid;   A 2  is selected from the group consisting of arginine, histidine, and lysine;   A 3  is selected from the group consisting of valine, alanine, isoleucine, and leucine;   A 4  is selected from the group consisting of tyrosine, phenylalanine, and tryptophan;   A 5  is selected from the group consisting of isoleucine, valine, alanine, and leucine;   A 6  is selected from the group consisting of histidine, arginine, and lysine;   A 7  is serine; and   A 8  is absent.   
     
     
         2 . The method of  claim 1 , wherein the painful condition is selected from the group consisting of acute pain, trauma-induced pain, dental pain, and osteoarthritis. 
     
     
         3 . The method of  claim 1 , wherein the oligopeptide is glycosylated with a monosaccharide or disaccharide. 
     
     
         4 . The method of  claim 3 , wherein at least one of the monosaccharides or disaccharides is selected from the group consisting of glucose, galactose, xylose, fucose, rhamnose, lactose, cellobiose, and melibiose. 
     
     
         5 . The method of  claim 1 , wherein A 7  is glycosylated. 
     
     
         6 . The method of  claim 5 , wherein A 7  is glycosylated with glucose or lactose. 
     
     
         7 . The method of  claim 1 , wherein A 7  is terminated with an amino group. 
     
     
         8 . The method of  claim 1 , wherein A 1  is alanine. 
     
     
         9 . The method of  claim 1 , wherein the oligopeptide comprises at least one D-amino acid. 
     
     
         10 . A method for treating a painful condition in a subject comprising administering a therapeutically effective amount of an oligopeptide having the formula: A 1 -A 2 -A 3 -A 4 -A 5 -A 6 -A 7 -A 8  (SEQ ID NO:1) wherein
 A 1  is selected from the group consisting of alanine and glutamic acid;   A 2  is selected from the group consisting of arginine, histidine, and lysine;   A 3  is selected from the group consisting of valine, alanine, isoleucine, and leucine;   A 4  is selected from the group consisting of tyrosine, phenylalanine, and tryptophan;   A 5  is selected from the group consisting of isoleucine, valine, alanine, and leucine;   A 6  is selected from the group consisting of histidine, arginine, and lysine;   A 7  is selected from the group consisting of proline and glycine; and   A 8  is serine.   
     
     
         11 . The method of  claim 10 , wherein the painful condition is selected from the group consisting of acute pain, trauma-induced pain, dental pain, and osteoarthritis. 
     
     
         12 . The method of  claim 10 , wherein the oligopeptide is glycosylated with a monosaccharide or disaccharide. 
     
     
         13 . The method of  claim 12 , wherein at least one of the monosaccharides or disaccharides is selected from the group consisting of glucose, galactose, xylose, fucose, rhamnose, lactose, cellobiose, and melibiose. 
     
     
         14 . The method of  claim 10 , wherein A 8  is glycosylated. 
     
     
         15 . The method of  claim 14 , wherein A 8  is glycosylated with glucose or lactose. 
     
     
         16 . The method of  claim 10 , wherein A 8  is terminated with an amino group. 
     
     
         17 . The method of  claim 10 , wherein A 1  is alanine. 
     
     
         18 . The method of  claim 10 , wherein the oligopeptide comprises at least one D-amino acid.