Bmp-2-binding peptide amphiphile nanofibers

Abstract

Provided herein are peptide amphiphiles with binding affinity for the bone promoting growth factor BMP-2, and methods of use thereof. In particular nanofibers and gel scaffolds of BMP-2-binding peptide amphiphiles are provided.

1 . A peptide amphiphile comprising:
 (a) a hydrophobic non-peptidic segment;   (b) a β-sheet-forming peptide segment;   (c) an acidic peptide segment; and   (d) a BMP-2 binding peptide;   wherein the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the β-sheet-forming peptide segment;   wherein the C-terminus of the β-sheet-forming peptide segment is covalently attached to the N-terminus of the acidic peptide segment; and   wherein the C-terminus of the acidic peptide segment is covalently attached to the N-terminus of the BMP-2 binding peptide.   
     
     
         2 . The peptide amphiphile of  claim 1 , wherein the hydrophobic non-peptidic segment comprises an acyl chain. 
     
     
         3 . The peptide amphiphile of  claim 2 , wherein the acyl chain comprises C 6 -C 20 . 
     
     
         4 . The peptide amphiphile of  claim 3 , wherein the acyl chain comprises lauric acid. 
     
     
         5 . The peptide amphiphile of  claim 1 , wherein the β-sheet-forming peptide segment comprises AAAVVV(SEQ ID NO:3). 
     
     
         6 . The peptide amphiphile of  claim 1 , wherein the acid peptide segment comprises a Glu (E) and/or Asp (D) residues. 
     
     
         7 . The peptide amphiphile of  claim 6 , wherein the acidic peptide segment comprises 2-7 amino acids in length with 50% or more amino acids selected from Glu (E) and/or Asp (D) residues. 
     
     
         8 . The peptide amphiphile of  claim 7 , wherein the acidic peptide segment comprises EEE. 
     
     
         9 . The peptide amphiphile of  claim 1 , wherein the binding sequence comprises a 6 amino acid segment with at least 50% sequence identity with TSPHVPYGGGS (SEQ ID NO:1). 
     
     
         10 . The peptide amphiphile of  claim 9 , wherein the binding sequence comprises TSPHVPYGGGS(SEQ ID NO:1). 
     
     
         11 . A self-assembled nanofiber comprising:
 (a) a first plurality of peptide amphiphiles comprising:
 (i) a hydrophobic non-peptidic segment; 
 (ii) a β-sheet-forming peptide segment; 
 (iii) an acidic peptide segment; and 
 (iv) a BMP-2 binding peptide; 
   wherein the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the β-sheet-forming peptide segment; wherein the C-terminus of the β-sheet-forming peptide segment is covalently attached to the N-terminus of the acidic peptide segment; and wherein the C-terminus of the acidic peptide segment is covalently attached to the N-terminus of the BMP-2 binding peptide; and   (b) a second plurality of peptide amphiphiles comprising:
 a hydrophobic non-peptidic segment; 
 (ii) a β-sheet-forming peptide segment; and 
 (iii) an acidic peptide segment; and 
   wherein the hydrophobic non-peptidic segment is covalently attached to the N-terminus of the β-sheet-forming peptide segment; wherein the C-terminus of the β-sheet-forming peptide segment is covalently attached to the N-terminus of the acidic peptide segment.   
     
     
         12 . The self-assembled nanofiber of  claim 11 , wherein (a) and (b) comprise the same a hydrophobic non-peptidic segments, β-sheet-forming peptide segments, and acidic peptide segments. 
     
     
         13 . The self-assembled nanofiber of  claim 11 , wherein the peptide amphiphile of (b) does not comprise a BMP-2 binding peptide, and the acidic peptide is the N-terminus of the peptide ampphiphile of (b). 
     
     
         14 . The self-assembled nanofiber of  claim 11 , wherein (a) and (b) are present at a ratio between 1:10 and 10:1. 
     
     
         15 . The self-assembled nanofiber of  claim 14 , wherein (a) and (b) are present at a ratio between 1:2 and 2:1. 
     
     
         16 . A gel scaffold comprising the self-assembled nanofibers of  claim 11 . 
     
     
         17 . A method of promoting osteogenesis comprising administering to a subject the self-assembled nanofibers of  claim 11 . 
     
     
         18 . A method of promoting arthrodesis comprising administering to a subject the self-assembled nanofibers of  claim 11 . 
     
     
         19 . A method of promoting spinal fusion comprising administering to a subject the self-assembled nanofibers of  claim 11 .