Self-Assembly of Peptide-Amphiphile Nanofibers Under Physiological Conditions

• US 20110008890A1
• Filed: 06/09/2010
• Published: 01/13/2011
• Est. Priority Date: 02/15/2002
• Status: Active Grant

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Hartgerink, Jeffrey D., Beniash, Elia, Stupp, Samuel I.
• Granted Patent: US 8,063,014 B2
• Time in Patent Office: Days
• US Class Current: 435/375
• 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: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: Y10S 977/705 Protein or peptide
• CPC Class Codes: Y10T 428/12014 having metal particles
• CPC Class Codes: Y10T 428/24413 Metal or metal compound

Abstract

Peptide amphiphile compounds, compositions and methods for self-assembly or nanofibrous network formation under neutral or physiological conditions.

Claims

1-33. -33. (canceled)

34. A method of promoting neuron growth and development comprising

(a) contacting cells with a peptide amphiphile molecule in an aqueous solution, wherein said peptide amphiphile molecule comprises a single C₆ to C₂₂ linear hydrocarbon segment covalently linked to a peptide segment comprising the bioactive epitope sequence IKVAV (SEQ ID NO:

1), and

(b) contacting said peptide amphiphile molecule with an effective amount of a metal ion sufficient to induce formation of a cylindrical micellar nanofiber composed of beta-sheets, wherein said nanofibers promotes neuron growth and development.

35. The method of claim 34, wherein said contacting step occurs under physiological conditions.

36. The method of claim 34, wherein said metal ion is present in a bodily fluid.

37. The method of claim 34, wherein said metal ion is selected from the group consisting of Ca, Mg, Cd, Fe, and Zn divalent ions, Al, Fe, and Gd trivalent ions, and combination of said ions.

38. The method of claim 34, wherein said peptide amphiphile molecule has a net charge at substantially physiological pH.

39. The method of claim 34, wherein said hydrocarbon segment is linked to the N-terminus of said peptide segment.

40. The method of claim 34, wherein said cylindrical micellar nanofiber has a conical shape comprised of a narrow hydrocarbon tail at one end and a bulkier peptide region at the other.

41. The method of claim 34, wherein said cylindrical micellar nanofiber displays a secondary structure that includes both beta-sheets and alpha-sheets.

42. The method of claim 34, wherein said administering comprises parenteral administration of an aqueous solution comprising said peptide amphiphile.

43. The method of claim 34, wherein said cells are further contacted with a therapeutic agent selected from the group consisting of growth factors, co-factors, and activators.