BONE SUBSTITUTE NANOCOMPOSITES AND METHODS OF SYNTHESIS USINGMULTIPHOSPHORYLATED PEPTIDES

• US 20150045304A1
• Filed: 11/13/2013
• Published: 02/12/2015
• Est. Priority Date: 11/13/2012
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: BENIASH, ELIA, SFEIR, CHARLES S.
• Granted Patent: US 9,221,888 B2
• Time in Patent Office: Days
• US Class Current: 514/16.7
• 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: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

The invention relates to peptides including DEDE(SSD)_nDEG indicated by SEQ NO. 1, RRRDEDE(SSD)_nDEG indicated by SEQ No. 2, RRRGDEDE(SSD)_nDEG indicated by SEQ No. 3, and LKKLKKLDEDE(SSD)nDEG indicated by SEQ NO. 4, wherein n is an integer from 2 to 20. The invention also relates to phosphorylating these peptides at multiple amino acid sites by employing casein kinases. These phosphorylated peptides may be used in various applications such as forming mineralized collagen fibrils and biometic composites for use in tissue repair and regeneration.

Claims

1. A peptide selected from the group consisting of:

DEDE(SSD)_nDEG, wherein n is an integer from 2 to 20, indicated by SEQ NO. 1;

RRRDEDE(SSD)_nDEG, wherein n is an integer from 2 to 20, indicated by SEQ NO. 2;

RRRGDEDE(SSD)_nDEG, wherein n is an integer from 2 to 20, indicated by SEQ NO. 3; and

LKKLKKLDEDE(SSD)_nDEG, wherein n is an integer from 2 to 20, indicated by SEQ NO. 4.

2. The peptide of claim 1, selected from the group consisting of:

DEDESSDSSDSSDDEG, indicated by SEQ NO. 1;

RRRDEDESSDSSDSSDDEG, indicated by SEQ NO. 2;

RRRDEDESSDSSDSSDSSDSSDDEG, indicated by SEQ NO. 2; and

RRRGDEDESSDSSDSSDDEG, indicated by SEQ NO. 3.

3. A mineralized collagen fibril which comprises collagen fibrils, organized mineral crystals and the peptide of claim 1 to promote the organized mineralization of collagen fibrils.

4. A biometic composite which comprises collagen fibrils, organized mineral crystals and the peptide of claim 1 to promote the organized mineralization of collagen fibrils.

5. A process for preparing a phosphorylated peptide, comprising:

faulting the peptide of claim 1; and

phosphorylating multiple amino acid sites of the peptide of claim 1.

6. The process of claim 5, wherein the phosphorylating of the peptide employs casein kinases.

7. The process of claim 6, wherein up to 80% of serines in the peptide are phosphorylated by casein kinases.

8. The process of claim 6, wherein the phosphorylating employs CK1, CK2 or a combination thereof.

9. The process of claim 5, wherein ATP is a source of phosphate.