Self-assembly and mineralization of peptide-amphiphile nanofibers

• US 7,491,690 B2
• Filed: 11/14/2002
• Issued: 02/17/2009
• Est. Priority Date: 11/14/2001
• Status: Expired due to Fees

• 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
• Primary Examiner(s): Gupta; Anish
• Application Number:
  US10/294,114
• Publication Number:
  US 20040018961A1
• Time in Patent Office: 2,287 Days
• Field of Search: 514/2, 514 12- 19, 514/762, 514/788.1, 514/944
• US Class Current: 514/1.1
• 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 amphiphile selected from the group consisting of

CCCCGGGSRGD (SEQ ID NO:

2),

CCCCGGGSRGDS (SEQ ID NO;

     17),

CCCCGGGSKGE (SEQ ID NO;

     11),

CCCCGGGEIKVAV (SEQ ID NO;

     16),

AAAAGGGSRGD (SEQ ID NO;

     9),

AAAAGGGSKGE (SEQ ID NO;

     12), and

GGGSRGD (SEQ ID NO;

     7),

wherein the serine residue in the peptide amphiphile is optionally phosphorylated and wherein a C₁₀-C₂₂ hydrocarbon component is attached to the N-terminus of the peptide component, which directs said composition to form a cylindrical micelle in an aqueous medium.

2. The peptide amphiphile composition of claim 1, wherein said peptide amphiphile is CCCCGGGEIKVAV (SEQ ID NO:

16).

3. The peptide amphiphile composition of claim 1, wherein said peptide amphiphile is AAAAGGGSRGD (SEQ ID NO:

2).

4. The peptide amphiphile composition of claim 3, wherein the serine residue of the peptide amphiphile is phosphorylated.

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

6. The system of claim 5 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.

7. The system of claim 5 wherein said reagent is a base, said pH is greater than about 4, and said system comprises a solution of said amphiphile composition.

8. The system of claim 7 further comprising an oxidizing agent to form a disulfide bond between amphiphile compositions.

9. The system of claim 8 further comprising a subsequent reducing agent to cleave said disulfide bond.

10. 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.

11. The template of claim 10 comprising a plurality of cysteine residues, wherein the thiol moieties thereof are oxidized to form a disulfide bond between amphiphile compositions.

12. The template of claim 10 wherein said peptide amphiphile component comprises at least one phosphoserine residue.

13. An organo-mineral composite comprising a nanofibrous micelle template of claim 12, and hydroxyapatite crystals on said micelle template, the c-axes of said crystals aligned substantially parallel with the longitudinal axis of said template.