Tricalcium phosphate binding peptides and uses thereof
The invention is directed to a composition comprising all or a portion of a beta-tricalcium phosphate (β-TCP) bound to all or a portion of a β-TCP binding peptide and methods of use thereof.
1. A composition comprising a beta-tricalcium phosphate (β-TCP) non-covalently bound to a concatenated multimer of two or more β-TCP binding peptides, wherein at least one of the β-TCP binding peptides comprises LLADTTHHRPWT (SEQ ID NO: 1), and binds to β-TCP with a Kd of 3.5 μM or lower.
2. The composition of claim 1 wherein the β-TCP is a β-TCP scaffold.
3. The composition of claim 2 wherein the scaffold further comprises polylactide-co-glycolide.
4. The composition of claim 2 wherein the scaffold further comprises one or more porogens.
5. The composition of claim 4 wherein the porogen is sucrose.
6. The composition of claim 1 wherein the composition is a concatenated multimer comprising two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, or twenty repeats of a β-TCP binding peptide bound to the β-TCP.
7. The composition of claim 1 wherein at least one of the β-TCP binding peptides comprises the amino acid sequence: GQVLPTTTPSSP (SEQ ID NO: 2), VPQHPYPVPSHK (SEQ ID NO: 3), HNMAPATLHPLP (SEQ ID NO: 4), QSFASLTNPRVL (SEQ ID NO: 5), HTTPTTTYAAPP (SEQ ID NO: 6), QYGVVSHLTHTP (SEQ ID NO: 7), TMSNPITSLISV (SEQ ID NO: 8), IGRISTHAPLHP (SEQ ID NO: 9), MNDPSPWLRSPR (SEQ ID NO: 10), QSLGSMFQEGHR (SEQ ID NO: 11), KPLFTRYGDVAI (SEQ ID NO: 12), MPFGARILSLPN (SEQ ID NO: 13), QLQLSNSMSSLS (SEQ ID NO: 14), TMNMPAKIFAAM (SEQ ID NO: 15), EPTKEYTTSYHR (SEQ ID NO: 16), DLNELYLRSLRA (SEQ ID NO: 17), DYDSTHGAVFRL (SEQ ID NO: 18), SKHERYPQSPEM (SEQ ID NO: 19), HTHSSDGSLLGN (SEQ ID NO: 20), NYDSMSEPRSHG (SEQ ID NO: 21), ANPIISVQTAMD (SEQ ID NO: 22) or a combination thereof.
8. The composition of claim 1 wherein one or more of the β-TCP binding peptides is fused to one or more additional peptides or proteins.
9. The composition of claim 8 wherein each β-TCP binding peptide is fused to each additional peptide or protein via a linker.
10. The composition of claim 8 wherein one or more of the β-TCP binding peptides is fused to all or a portion of a growth factor or a cytokine.
11. The composition of claim 8 wherein the one or more additional peptides or proteins is an epidermal growth factor (EGF), a platelet-derived growth factor (PDGF), a bone morphogenic protein 2 (BMP-2), BMP-4, BMP-7, osteogenic protein (OP-1), collagen binding protein or a combination thereof.
12. The composition of claim 9 wherein the linker is a coiled coil linker.
13. The composition of claim 12 wherein the coiled coil linker is a leucine zipper.
14. The composition of claim 1 wherein the composition further comprises mesenchymal stem cells.
15. A pharmaceutical composition comprising the composition of claim 1 .
16. The composition of claim 2 , wherein the (β-TCP scaffold is in the shape of a cross having at least one dimension that is 3 mm in size.
17. The composition of claim 16 , wherein the cross has the dimensions 5 mm×5 mm×3 mm.
18. The composition of claim 2 , wherein the (β-TCP scaffold comprises granulated β-TCP powder that is at least 95% β-TCP.
19. The composition of claim 1 , wherein each β-TCP binding peptide comprises LLADTTHHRPWT (SEQ ID NO: 1), and binds to (β-TCP with a Kd of 3.5 μM or lower.