Self-assembly of peptide-amphiphile nanofibers under physiological conditions

• US 7,371,719 B2
• Filed: 02/18/2003
• Issued: 05/13/2008
• Est. Priority Date: 02/15/2002
• Status: Expired due to Term

• Current Assignee: Northwestern University
• Original Assignee: Northwestern University
• Inventors: Stupp, Samuel I., Hartgerink, Jeffrey D., Beniash, Elia
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): LIU, SAMUEL W
• Application Number:
  US10/368,517
• Publication Number:
  US 20040001893A1
• Time in Patent Office: 1,911 Days
• Field of Search: 514/2, 514/492, 530/300, 530/350, 530/378.3, 530/402, 424/1.65
• US Class Current: 424/185.1
• 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: 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. A sol-gel composition comprising (i) a peptide amphiphile compound having a net charge at physiological pH which comprises a peptide component containing a peptidic epitope sequence, a hydrophobic component which is not peptide, and residues for intermolecular disulfide bond formation, wherein said epitope sequence is selected from RGD, IKVAV (SEQ ID NO:

45) and YIGSR (SEQ ID NO;

46), and (ii) a metal ion to induce gelation of said amphiphile compound whereby the composition forms a gel of supramolecular nanofibers of said amphiphile compound in the presence of said reagent, wherein said reagent comprises metal ion in stoichiometric excess of said amphiphile compound.

2. The composition of claim 1 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 combinations of said ions.

3. The composition of claim 1 wherein said residues comprise cysteine residues which form one or more disulfide bonds, said composition further comprises an oxidizing agent to form said disulfide bonds between amphiphile compounds.

4. The composition of claim 3 further comprising a subsequent reducing agent to cleave said disulfide bond.

5. The composition of claim 1 wherein said reagent is a metal hydroxide.