# US 10,765,748 B2 · Composition and methods for tethering bioactive peptides to metal oxide surfaces

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,765,748 B2
- Document ID: US10765748B2
- Status: Granted
- Kind: B2
- Application number: 15/325,218
- Filed: 2015-07-13
- Published: 2017-07-06
- Granted: 2020-09-08
- Earliest claimed: 2014-07-11
- Assignees: The University of Akron
- Applicants: Matthew Becker; Wen Tang
- Inventors: Matthew Becker; Wen Tang
- Web page: https://patentgrep.com/patent/US10765748B2

## CPC

- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/51: Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

In various aspects, embodiments of the present invention are directed to a series of multivalent dendrons containing a bioactive peptide domain and surface-binding catechol domains. In some embodiments, these multivalent dendrons were obtained through solid phase synthesis and have a strong binding affinity to metal oxide surfaces such as, TiO2, ZrO2, CeO2, and Fe3O4, SiO2, as well as other inorganic surfaces such as hydroxyapatite, silver, fluorapatite, calcium carbonate and gold. These catechol-bearing dendrons provide a fast and efficient method to functionalize a wide range of inorganic materials with bioactive peptides and have the potential to be used in coating orthopaedic implants and fixation devices.

## Claims

### Claim 1

A multivalent dendron comprising a bioactive peptide domain and one or more surface-binding catechol domains and having the formula:
wherein PEP is a bioactive peptide domain of 2-30 amino acids having a specific biological function; R is selected from the group consisting of —CH3, —(CH2)3NHC(NH2)C═NH, —CH2CONH2, —CH2COOH, —CH2SH, —(CH2)2COOH, —(CH2)2CONH2, —NH2, —CH2C═CH—N═CH—NH, —CH(CH3)CH2CH3, —CH2CH(CH3)2, —(CH2)4NH2, —(CH2)2SCH3, —CH2Ph, —CH2OH, —CH(OH)CH3, —CH2—C═CH—NH-Ph, —CH2-Ph-OH, —CH(CH3)2, and combinations thereof; a is an integer from 1 to 20; and m is 0 or 1.

### Claim 2

A lysine-based multivalent dendron comprising a bioactive peptide domain and one or more surface-binding catechol domains and having the formula:
wherein PEP is a bioactive peptide domain of 2-30 amino acids having a specific biological function; a is an integer from 1 to 20 and m is 0 or 1.

### Claim 3

A lysine-based multivalent dendron comprising a bioactive peptide domain and one or more surface-binding catechol domains and having the formula:
wherein PEP is a bioactive peptide domain of 2-30 amino acids having a specific biological function; a is an integer from 1 to 20; and m is 0 or 1.

### Claim 4

A lysine-based multivalent dendron having the formula:
wherein PEP is a bioactive peptide; a is an integer from 1 to 20 and m is 0 or 1.

### Claim 5 (depends on 4)

The multivalent dendron of claim 4 wherein said bioactive peptide is selected from the group consisting of: —NH-KIPKASSVPTELSAISTLYL-COOH (SEQ ID No. 1), BMP-2, OGP, OGP C-terminal sequence YGFGG (SEQ ID No. 8), GRGDS (SEQ. ID No. 9), and combinations thereof.

### Claim 6 (depends on 4)

The multivalent dendron of claim 4 wherein said bioactive peptide is less than 30 amino acids in length.

### Claim 7 (depends on 4)

The multivalent dendron of claim 4 wherein said bioactive peptide is OGP C-terminal sequence YGFGG (SEQ ID No. 8).

### Claim 8

A lysine-based multivalent dendron having the formula:
wherein PEP is a bioactive peptide; a is an integer from 1 to 20; and m is 0 or 1.

### Claim 9 (depends on 8)

The multivalent dendron of claim 8 wherein said bioactive peptide is selected from the group consisting of: —NH-KIPKASSVPTELSAISTLYL-COOH (SEQ ID No. 1), BMP-2, OGP, OGP C-terminal sequence YGFGG (SEQ ID No. 8), GRGDS (SEQ. ID No. 9), and combinations thereof.

### Claim 10 (depends on 8)

The multivalent dendron of claim 8 wherein said bioactive peptide is less than 30 amino acids in length.

### Claim 11 (depends on 8)

The multivalent dendron of claim 8 wherein said bioactive peptide is OGP C-terminal sequence YGFGG (SEQ ID No. 8).

### Claim 12 (depends on 2)

The lysine-based multivalent dendron of claim 2 having the formula:
wherein PEP is a bioactive peptide domain of 2-30 amino acids having a specific biological function; a is an integer from 1 to 20 and m is 0 or 1.

### Claim 13 (depends on 12)

The lysine-based multivalent dendron of claim 12 wherein said bioactive peptide is selected from the group consisting of: —NH-KIPKASSVPTELSAISTLYL-COOH (SEQ ID No. 1), BMP-2, OGP, OGP C-terminal sequence YGFGG (SEQ ID No. 8), GRGDS (SEQ. ID No. 9), and combinations thereof.

### Claim 14 (depends on 12)

The lysine-based multivalent dendron of claim 12 wherein said bioactive peptide is OGP C-terminal sequence YGFGG (SEQ ID No. 8).

### Claim 15 (depends on 2)

The lysine-based multivalent dendron of claim 2 having the formula:
wherein PEP is a bioactive peptide domain of 2-30 amino acids having a specific biological function; a is an integer from 1 to 20 and m is 0 or 1.

### Claim 16 (depends on 15)

The lysine-based multivalent dendron of claim 15 wherein said bioactive peptide is selected from the group consisting of: —NH-KIPKASSVPTELSAISTLYL-COOH (SEQ ID No. 1), BMP-2, OGP, OGP C-terminal sequence YGFGG (SEQ ID No. 8), GRGDS (SEQ. ID No. 9), and combinations thereof.

### Claim 17 (depends on 15)

The lysine-based multivalent dendron of claim 15 having the formula:
where PEP is a bioactive peptide; a is an integer from 1 to 20; and m is 0 or 1.

### Claim 18 (depends on 17)

The lysine-based multivalent dendron of claim 17 wherein said bioactive peptide is selected from the group consisting of: —NH-KIPKASSVPTELSAISTLYL-COOH (SEQ ID No. 1), BMP-2, OGP, OGP C-terminal sequence YGFGG (SEQ ID No. 8), GRGDS (SEQ. ID No. 9), and combinations thereof.

### Claim 19 (depends on 15)

The lysine-based multivalent dendron of claim 15 having the formula:
where PEP is a bioactive peptide; a is an integer from 1 to 20; and m is 0 or 1.

### Claim 20 (depends on 19)

The lysine-based multivalent dendron of claim 19 wherein said bioactive peptide is selected from the group consisting of: —NH-KIPKASSVPTELSAISTLYL-COOH (SEQ ID No. 1), BMP-2, OGP, OGP C-terminal sequence YGFGG (SEQ ID No. 8), GRGDS (SEQ. ID No. 9), and combinations thereof.