Self-assembly of peptide-amphiphile nanofibers under physiological conditions

• US 8,063,014 B2
• Filed: 06/09/2010
• Issued: 11/22/2011
• Est. Priority Date: 02/15/2002
• Status: Expired due to Fees

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Stupp, Samuel I., Hartgerink, Jeffrey D., Beniash, Elia
• Primary Examiner(s): Desai; Anand
• Assistant Examiner(s): Liu; Samuel
• Application Number:
  US12/797,586
• Publication Number:
  US 20110008890A1
• Time in Patent Office: 531 Days
• Field of Search: None
• US Class Current: 514/2
• 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

The present invention provides a method of promoting neuron growth and development by contacting cells with a peptide amphiphile molecule in an aqueous solution in the presence of a metal ion. According to the method, the peptide amphiphile forms a cylindrical micellar nanofiber composed of beta-sheets, which promote neuron growth and development.

Claims

1. A method of promoting neuron growth and development comprising

(a) contacting neurons undergoing neuron growth and development 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 selected from Ca^2+, Mg^2+,, Fe^2+,, Zn^2+,, and Fe³⁺, and combinations thereof sufficient to induce formation of a cylindrical micellar nanofiber composed of beta-sheets, wherein said nanofibers promote the neuron growth and development.

2. The method of claim 1, wherein said contacting step occurs under physiological conditions.

3. The method of claim 1, wherein said metal ion is present in a bodily fluid.

4. The method of claim 1, wherein said peptide amphiphile molecule has a net charge at substantially physiological pH.

5. The method of claim 1, wherein said hydrocarbon segment is linked to the N-terminus of said peptide segment.

6. The method of claim 1, 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.

7. The method of claim 1, wherein said cylindrical micellar nanofiber displays a secondary structure that includes both beta-sheets and alpha-helices.

8. The method of claim 1, wherein said contacting said neurons undergoing neuron growth and development with said peptide amphiphile administering comprises parenteral administration of an aqueous solution comprising said peptide amphiphile.

9. The method of claim 1, wherein said neurons undergoing neuron growth and development are further contacted with a therapeutic agent selected from the group consisting of growth factors, co-factors, and activators.

10. A method of promoting neuron growth and development comprising

(a) contacting neurons undergoing neuron growth and development 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 Ca²⁺ sufficient to induce formation of a cylindrical micellar nanofiber composed of beta-sheets, wherein said nanofibers promote the neuron growth and development.