Biologically active silver-coated proteins

• US 9,057,088 B2
• Filed: 01/26/2006
• Issued: 06/16/2015
• Est. Priority Date: 01/26/2005
• Status: Expired due to Fees

• Current Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Original Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Inventors: Freeman, Amihay, Shacham-Diamand, Yosi, Moscovich-Dagan, Hila, Hadar, Noa
• Primary Examiner(s): SINGH, SATYENDRA K
• Application Number:
  US11/795,924
• Publication Number:
  US 20090291070A1
• Time in Patent Office: 3,428 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: C07K 14/00 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Silver-coated proteins, being dissolvable or suspendable in aqueous media and/or retaining a biological activity of the protein and a process for preparing same are disclosed. Further disclosed are modified proteins which have a reducing moiety attached to the surface thereof and a process for preparing same. The modified proteins can be utilized for obtaining the silver-coated proteins. Further disclosed are a pharmaceutical composition containing and a method of treating bacterial and fungal infections utilizing biologically active silver-coated hydrogen peroxide producing enzymes such as glucose oxidase. Further disclosed are conductive elements that comprise the silver-coated proteins disclosed herein and electronic circuits containing same. Further disclosed are electrodes having the silver-coated proteins deposited thereon and biosensor systems utilizing same for determining a level of an analyte in a liquid sample.

Claims

1. A composition-of-matter comprising a protein having a solvent-accessible surface and further having a biological activity and a metallic silver coating deposited over said surface and forming a silver-coated protein retaining said biological activity, wherein said protein has at least one oxidized reducing moiety attached to at least a portion of said surface, said reducing moiety being selected from the group consisting of hydrazine, hydrazide and imine, said oxidized reducing moiety being obtained upon reducing silver ions to form said metallic silver coating, said silver coating is in a form of a continuous metallic silver layer covering 0.1% to 60% of said surface, and wherein said protein is a hydrogen peroxide producing enzyme and said biological activity is a catalytic reaction activity.

2. The composition-of-matter of claim 1, wherein said silver-coated protein is dissolvable or suspendable in an aqueous medium.

3. A pharmaceutical composition for the treatment of a bacterial and/or fungal infection, comprising, as an active ingredient, the composition-of-matter of claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition of claim 3, packaged in a packaging material and identified in print, in or on said packaging material, for treatment of said infection.

5. The composition-of-matter of claim 1, wherein said reducing moiety is imine.

6. The composition-of-matter of claim 5, wherein said protein having an oxidized imine attached to at least a portion of a surface thereof is obtained upon conjugating a polyaldehyde to said protein'"'"'s surface.

7. The composition-of-matter of claim 1, wherein said reducing moiety is selected from the group consisting of hydrazide and imine.

8. The composition-of-matter of claim 7, wherein said oxidized reducing moiety is attached to said surface via an aldehyde group generated on said surface.

9. The composition-of-matter of claim 8, wherein said reducing moiety is formed upon conjugating a chemical moiety to said aldehyde group.

10. The composition-of-matter of claim 9, wherein said chemical moiety is selected from the group consisting of β

-alanine and adipic-dihydrazide.

11. A process of preparing the composition-of-matter of claim 1, the process comprising:

providing a first aqueous solution containing silver ions;

providing a protein having a first reactive group on a surface thereof;

conjugating to said first reactive group a first chemical moiety selected such that upon said conjugating a protein having said reducing moiety attached to said surface is obtained, said reducing moiety being selected from the group consisting of hydrazine, hydrazide and imine; and

contacting said protein having said reducing moiety attached to said surface with said first aqueous solution, to thereby form said silver-coated protein, thereby obtaining the composition-of-matter.

12. The process of claim 11, wherein a substrate of said hydrogen peroxide producing enzyme is a sugar.

13. The process of claim 12, wherein said sugar is glucose.

14. The process of claim 13, wherein said enzyme is glucose oxidase.

15. A method of treating a bacterial and/or fungal infection, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising the composition-of-matter of claim 1.

16. The method of claim 15, wherein a substrate of said hydrogen peroxide producing enzyme is a sugar.

17. The method of claim 16, wherein said sugar is glucose.

18. The method of claim 17, wherein said enzyme is glucose oxidase.