Peptide nanostructures containing end-capping modified peptides and methods of generating and using the same

• US 7,786,086 B2
• Filed: 09/08/2005
• Issued: 08/31/2010
• Est. Priority Date: 09/08/2004
• 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: Reches, Meital, Gazit, Ehud
• Primary Examiner(s): Gupta; Anish
• Assistant Examiner(s): Cordero Garcia; Marcela M
• Application Number:
  US11/662,136
• Publication Number:
  US 20080009434A1
• Time in Patent Office: 1,818 Days
• Field of Search: None
• US Class Current: 530/300
• 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 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 14/001 by chemical synthesis
• CPC Class Codes: C07K 5/06078 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/06191 containing heteroatoms different from O, S, or N
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 25/14 Scaffolds; Matrices in general C12N5/0068
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: C12Q 2563/155 Particles of a defined size, e.g. nanoparticles
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: Y10T 428/298 Physical dimension
• CPC Class Codes: Y10T 442/614 Strand or fiber material specified as having microdimensions [i.e., microfiber]

Abstract

A nanostructure composed of a plurality of peptides, each peptide containing at least one aromatic amino acid, whereby one or more of these peptides is end-capping modified, is disclosed. The nanostructure can take a tubular, fibrillar, planar or spherical shape, and can encapsulate, entrap or be coated by other materials. Methods of preparing the nanostructure, and devices and methods utilizing same are also disclosed.

Claims

1. A nanostructure composed of a plurality of aromatic homodipeptides, wherein at least one of said homodipeptides is an end-capping modified peptide, the nanostructure being selected from the group consisting of a discrete fibrillar nanostructure, a discrete tubular nanostructure and a discrete spherical nanostructure.

2. The nanostructure of claim 1, wherein said end capping modified peptide comprises at least one end capping moiety, said end capping moiety being selected from the group consisting of an aromatic end capping moiety and a non-aromatic end-capping moiety.

3. The nanostructure of claim 2, wherein said end-capping moiety comprises a labeling moiety.

4. The nanostructure of claim 2, wherein said end capping moiety is an aromatic moiety and the nanostructure is a fibrillar nanostructure.

5. The nanostructure of claim 2, wherein said aromatic end capping moiety is selected from the group consisting of 9-fluorenylmethyloxycarbonyl (Fmoc) and benzyloxycarbonyl (Cbz).

6. The nanostructure of claim 2, wherein said end-capping moiety is a non-aromatic moiety and the nanostructure is a discrete tubular nanostructure or a discrete spherical nanostructure.

7. The nanostructure of claim 2, wherein said non-aromatic end capping moiety is selected from the group consisting of acetyl and tert-butoxycarbonyl (Boc).

8. The nanostructure of claim 1, wherein said homodipeptide is selected from the group consisting of naphthylalanine-naphthylalanine dipeptide, (pentafluro-phenylalanine)-(pentafluro-phenylalanine) dipeptide, (iodo-phenylalanine)-(iodo-phenylalanine) dipeptide, (4-phenyl phenylalanine)-(4-phenyl phenylalanine) dipeptide and (p-nitro-phenylalanine)-(p-nitro-phenylalanine) dipeptide.

9. The nanostructure of claim 1, wherein said end-capping modified peptide has the general Formula I:

R₁-[A₁]-[A₂]-R₂ 

 

Formula I

wherein;

each of A₁ and A₂ is an aromatic amino acid residue being the same;

R₁ is selected from the group consisting of N-terminus amine and an N-terminus end-capping moiety; and

R₂ is elected from the group consisting of C-terminus carboxylic acid and a C-terminus end-capping moiety, provided that at least one of R₁ and R₂ is an end capping moiety.

10. A method of generating the nanostructure of claim 1, the method comprising incubating a plurality of aromatic homodipeptides under conditions which favor formation of said nanostructure, wherein at least one aromatic homodipeptide is an end capping modified peptide.

11. A composition comprising a material at least partially enclosed by the nanostructure of claim 1.

12. A method of encapsulating a material in a nanostructure, the method comprising:

(a) providing the nanostructure of claim 1, the nanostructure having an internal cavity; and

(b) introducing the material into said internal cavity of the nanostructure, thereby encapsulating the material in the nanostructure.

13. A method of encapsulating material in a nanostructure, the method comprising assembling the nanostructure of claim 1 in the presence of the material, thereby encapsulating the material in the nanostructure.

14. A composition comprising:

(i) the nanostructure of claim 1; and

(ii) an agent being attached to said nanostructure.

15. The composition of claim 14, wherein said agent is entrapped within said nanostructure.

16. The composition of claim 14, wherein said nanostructure is biodegradable.

17. The composition of claim 14, wherein said agent is selected from the group consisting of a drug, a nucleic acid molecule and a polypeptide.

18. A fiber comprising a plurality of nanostructures, wherein each nanostructure of said plurality of nanostructures is the nanostructure of claim 1, the fiber being at least 100 nm in length.

19. A composition comprising a polymer and the nanostructure of claim 1.

20. A composition comprising a matrix and a plurality of the nanostructures of claim 1 dispersed throughout said matrix.