Finger-1 Peptide Analogs of the TGF-Beta Superfamily

Abstract

Members of the TGF-β superfamily and peptide fragments based on member proteins are employed to purify solutions containing member proteins or as therapeutics.

1 . An isolated polypeptide consisting of an active fragment of at least 8 consecutive amino acid residues of an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11; SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, wherein the polypeptide has the ability to bind to and stabilize a TGF-β superfamily member protein in solution. 
     
     
         2 . An isolated polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:11; SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23. 
     
     
         3 . An isolated polypeptide consisting of an amino acid sequence having at least 75% identity to the polypeptide of  claim 2 , wherein the polypeptide has the ability to bind to and stabilize a TGF-β superfamily member protein in solution. 
     
     
         4 . A composition comprising the polypeptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         5 . The composition of  claim 4 , wherein the carrier is selected from the group consisting of at least one of solvent, gel, polymer, demineralized bone, suture, surgical mesh, ceramic, micelle, buffer, collagen, collagen sponge, and cellulose. 
     
     
         6 . A chromatography media comprising the polypeptide of  claim 1 . 
     
     
         7 . A method of purifying a TGF-β superfamily member protein from a sample comprising:
 (a) providing the polypeptide of  claim 1  immobilized on a chromatography medium;   (b) incubating the medium with the sample; and   (c) eluting the protein from the medium.   
     
     
         8 . The method of  claim 7 , wherein the TGF-β superfamily member protein is a bone morphogenetic protein (BMP) or a growth differentiation factor (GDF). 
     
     
         9 . The method of  claim 8 , wherein the BMP is BMP-2. 
     
     
         10 . A method of stabilizing a solution containing a TGF-β superfamily member protein comprising adding a polypeptide of  claim 1  to the solution, wherein the ratio of the polypeptide to the protein is at least about 1:1, 2:1, 5:1, 10:1, 20:1, or 30:1. 
     
     
         11 . The method of  claim 10 , wherein the TGF-β superfamily member protein is a bone morphogenetic protein (BMP) or a growth differentiation factor (GDF). 
     
     
         12 . The method of  claim 11 , wherein the BMP is BMP-2.