BMP-2-BINDING PEPTIDE AMPHIPHILE NANOFIBERS
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 .