TGF-beta inhibitors and methods

Abstract

A family of small peptides have been found to be inhibitory to TGF-β activity, and preferably have the primary structure of Formula 1: Formula I AA 1 -AA 2 -AA 3 -Pro-D-Glu-Ala wherein AA 1 is leucine, phenylalanine, α-aminoisobutric acid, N-methylalanine, N-methylisoleucine, or isoleucine; AA 2 is the same or a different amino acid residue as in AA 1 ; and AA 3 is alanine or N-methylalanine.

It is claimed:  
     
         1 . A peptide having the primary structure of Formula I 
         
       AA 1 -AA 2 -AA 3 -Pro-D-Glu-Ala  Formula I  
       wherein AA 1  is leucine, phenylalanine, α-aminoisobutric acid, N-methylalanine, N-methylisoleucine, or isoleucine; AA 2  is the same or a different amino acid residue as in AA 1 ; and AA 3  is alanine or N-methylalanine.  
     
     
         2 . The peptide Leu-Ile-Ala-Pro-D-Glu-Ala.  
     
     
         3 . The peptide Phe-Ile-Ala-Pro-D-Glu-Ala.  
     
     
         4 . The peptide Leu-Phe-Ala-Pro-D-Glu-Ala.  
     
     
         5 . A therapeutic composition, comprising: 
       AA 1 -AA 2 -AA 3 -Pro-D-Glu-Ala  Formula I  
       wherein AA 1  is leucine, phenylalanine, α-aminoisobutric acid, N-methylalanine, N-methylisoleucine, or isoleucine, AA 2  is the same or a different amino acid residue as in AA 1 ; and AA 3  is alanine or N-methylalanine; and, 
 a physiologically acceptable carrier.  
 
     
     
         6 . The composition as in  claim 5  wherein the peptide includes Leu-Ile-Ala-Pro-D-Glu-Ala.  
     
     
         7 . The composition as in  claim 5  wherein the peptide includes Phe-Ile-Ala-Pro-D-Glu-Ala.  
     
     
         8 . The composition as in  claim 5  wherein the peptide includes Leu-Phe-Ala-Pro-D-Glu-Ala.  
     
     
         9 . The composition as in  claim 5  wherein the carrier is suitable for topical administration.  
     
     
         10 . A method of inhibiting TGF-β, comprising: 
 administering to a patient in need thereof an effective activity-inhibiting amount of a peptide specific against a fibrotic growth factor, the peptide having the primary structure 
 AA 1 -AA 2 -AA 3 -Pro-D-Glu-Ala  Formula I  
 wherein AA, is leucine, phenylalanine, α-aminoisobutric acid, N-methylalanine, N-methylisoleucine, or isoleucine; AA 2  is the same or a different amino acid residue as in AA 1 ; and AA 3  is alanine or N-methylalanine.  
 
     
     
         11 . The method as in  claim 10  wherein the peptide is effective in inhibiting TGF β-1.  
     
     
         12 . The method as in  claim 10  wherein the peptide includes Leu-Ile-Ala-Pro-D-Glu-Ala.  
     
     
         13 . The method as in  claim 10  wherein the peptide includes Phe-Ile-Ala-Pro-D-Glu-Ala.  
     
     
         14 . The method as in  claim 10  wherein the peptide includes Leu-Phe-Ala-Pro-D-Glu-Ala.  
     
     
         15 . The method as in  claim 10  wherein the administering is topical application.  
     
     
         16 . The method as in  claim 15  wherein the peptide is effective to inhibit scar tissue during wound healing.