Amyloid beta peptides and methods of use

• US 8,188,046 B2
• Filed: 10/12/2007
• Issued: 05/29/2012
• Est. Priority Date: 10/16/2006
• Status: Active Grant

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Cao, Chuanhai
• Primary Examiner(s): Kolker, Daniel E
• Application Number:
  US12/444,647
• Publication Number:
  US 20100172879A1
• Time in Patent Office: 1,691 Days
• Field of Search: None
• US Class Current: 514/17.8
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein

Abstract

The application describes several mutant amyloid beta peptides and specific regions which are useful in the therapeutic and diagnostic of neurological diseases. The application further describes methods of using these mutant peptides as treatment and reagents for diagnosis of diseases. The application further describes diagnostic kits and pharmaceutical compositions for use in therapy to treat neurological diseases including but not limited to Alzheimer'"'"'s disease and various forms of mild cognitive impairments.

Claims

1. An isolated peptide comprising an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRIIDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

2. The isolated peptide of claim 1, wherein said peptide consists of an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), or DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), or DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), or DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

3. The isolated peptide of claim 1, wherein said peptide comprises the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO;

1).

4. The isolated peptide of claim 1, wherein said peptide comprises the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2).

5. The isolated peptide of claim 1, wherein said peptide comprises the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3).

6. The isolated peptide of claim 1, wherein said peptide comprises the amino aid sequence:

DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4).

7. The isolated peptide claim 1, wherein said peptide comprises the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

8. The isolated peptide of claim 1, wherein said peptide consists of the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO;

1).

9. The isolated peptide of claim 1, wherein said peptide consists of the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2).

10. The isolated peptide of claim 1, wherein said peptide consists of the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3).

11. The isolated peptide of claim 1, wherein said peptide consists of the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4).

12. The isolated peptide claim 1, wherein said peptide consists of the amino acid sequence:

DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

13. A pharmaceutical composition comprising a peptide and a pharmaceutically acceptable carrier or pharmaceutical excipient, wherein said peptide comprises an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

14. The pharmaceutical composition of claim 13, wherein said peptide consists of an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), or DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), or DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), or DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

15. A kit comprising a peptide and a pharmaceutically acceptable carrier or pharmaceutical excipient, wherein said peptide comprises an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

16. The kit of claim 15, wherein said peptide consists of an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), or DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), or DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), or DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

17. An isolated polynucleotide comprising a nucleic acid sequence encoding a peptide comprising an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

18. The isolated polynucleotide of claim 17, wherein said peptide consists of an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), or DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), or DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), or DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

19. A method of treating Alzheimer'"'"'s in a mammal, comprising administering an effective amount of a peptide to the mammal, wherein the peptide comprises an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

21. The method of claim 19, wherein said peptide consists of an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), or DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), or DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), or DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

20. A method of treating Alzheimer'"'"'s in a mammal, comprising administering an effective amount of a dendritic cell to the mammal, wherein the dendritic cell has been pulsed with a peptide comprising an amino acid sequence selected from among DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24G) (SEQ ID NO;

3), DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).

22. The method of claim 20, wherein said peptide consists of an amino acid sequence DAEFRHDSGYEVHHQKLVFFAWDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22W) (SEQ ID NO:

1), or DAEFRHDSGYEVHHQKLVFFAEDMGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P24M) (SEQ ID NO;

2), or DAEFRHDSGYEVHHQKLVFFAEDGGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P240) (SEQ ID NO;

3), or DAEFRHDSGYEVHHQKLVFFAFDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22F) (SEQ ID NO;

4), or DAEFRHDSGYEVHHQKLVFFARDVGSNKGAIIGLMVGGVVIA (Amyloid beta mutant P22R) (SEQ ID NO;

5).