Self-assembly and mineralization of peptide-amphiphile nanofibers

• US 20040018961A1
• Filed: 11/14/2002
• Published: 01/29/2004
• Est. Priority Date: 11/14/2001
• Status: Active Grant

• Current Assignee: United States Air Force (Government of the United States of America)
• Original Assignee: Northwestern University
• Inventors: Stupp, Samuel I., Hartgerink, Jeffrey D., Beniash, Elia
• Granted Patent: US 7,491,690 B2
• Time in Patent Office: Days
• US Class Current: 514/7
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 47/6919 the form being a ribbon or a tubule cochleate
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 5/101 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

Peptide-amphiphilic compositions capable of self-assembly into useful nanostructures.

Claims

1. A peptide amphiphile composition comprising a peptide component

with a cell adhesion sequence;

and a hydrophobic component, said hydrophobic component sufficient to afford micelle formation of said composition in an aqueous medium.

2. The composition of claim 1 wherein said adhesion sequence comprises RGD.

3. The composition of claim 1 wherein said adhesion sequence comprises IKVAV.

4. The composition of claim 1 wherein said peptide component further includes at least one phosphorylated residue.

5. The composition of claim 4 wherein said phosphorylated residue is phosphoserine.

6. The composition of claim 1 wherein said peptide component further

comprises a residue with a functional moiety capable of intermolecular covalent bond formation.

7. The composition of claim 6 wherein said residue is cysteine.

8. The composition of claim 7 wherein said peptide component further comprises at least one phosphoserine residue.

9. The composition of claim 8 wherein said peptide component further

comprises at least one glycine residue between said cysteine and phosphoserine residues.

10. The composition of claim 8 wherein said cell adhesion sequence comprises RGD.

11. The composition of claim 10 wherein said hydrophobic component comprises an alkyl moiety of at least 6 carbon units.

12. The composition of claim 11 assembled into a cylindrical micelle.

13. The composition of claim 1 where in said peptide component is absent a cysteine residue.

14. The composition of claim 13 wherein said peptide component comprises an LLLKK sequence.

15. The composition of claim 13 wherein said peptide component comprises an LSL sequence.

16. The composition of claim 13 wherein said peptide component comprises an LSLS sequence.

17. The composition of claim 13 wherein said peptide component comprises an AAAAGGG sequence.

18. The composition of claim 13 wherein said cell adhesion sequence is selected from RGD, IKVAV and YIGSR.

19. The composition of claim 18 wherein said peptide component comprises at least one phosphorylated residue.

20. A sol-gel system comprising a solvent medium comprising a peptide amphiphile composition of claims-1, and a reagent to adjust system pH.

21. The system of claim 20 wherein said reagent is an acid, said pH is less than about 4, and said system comprises a gel of cylindrical micelles of said amphiphile composition.

22. The system of claim 21 wherein said reagent is a base, said pH is greater than about 4, and said system comprises a solution of said amphiphile composition.

23. The system of claim 20 wherein said peptide component of said amphiphile composition comprises a residue with a functional moiety capable of intermolecular covalent bond formation.

24. The system of claim 23 wherein said residue is cysteine.

25. The system of claim 24-further comprising an oxidizing agent to form a disulfide bond between amphiphile compositions.

26. The system of claim 25 further comprising a subsequent reducing agent to cleave said disulfide bond.

27. A nanofibrous micelle template for crystal growth, said template comprising an amphiphile composition of claim 1, said peptide component of said composition comprising a residue with a functional moiety capable of intermolecular covalent bond formation.

28. The template of claim 27 comprising a plurality of cysteine residues, wherein the thiol moieties thereof are oxidized to form a disulfide bond between amphiphile compositions.

29. The template of claim 27 wherein said peptide component further comprises at least one phosphorylated residue.

30. The template of claim 29 wherein said phosphorylated residue is phosphoserine.

31. The template of claim 30 wherein said peptide adhesion sequence comprises RGD.

32. An organo-mineral composite comprising a nanofibrous micelle template of claim 30, and hydroxyapatite crystals on said micelle template, the c-axes of said crystals aligned substantially parallel with the longitudinal axis of said template.

33. A method of using a peptide amphiphile composition to control hydroxyapatite crystal growth, said method comprising:

providing a solvent medium with at least one peptide amphiphile composition, each said composition comprising a peptide component with a cell adhesion sequence and a hydrophobic component sufficient to afford micelle formation of said composition in said medium, said peptide component further comprising a phosphorylated residue and a cysteine residue;

inducing assembly of said peptide amphiphile compositions into cylindrical micelles;

stabilizing said micelles with intermolecular covalent bond formation; and

introducing reagents for the preparation of hydroxyapatite.

34. The method of claim 33 wherein micelle assembly is induced by adjusting the pH of said medium to less than about 4.

35. The method of claim 33 wherein micelles are stabilized by intermolecular oxidative coupling and disulfide bond formation.