Peptides that bind to amino-truncated amyloid-beta-peptide and use of said peptides

Patent metadata

Field	Value
Publication number	US-9611296-B2
Application number	US-201314439895-A
Country	US
Kind code	B2
Filing date	Sep 25, 2013
Priority date	Nov 2, 2012
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

Peptides that bind to amino-terminal truncated pEAβ3-42, the free glutamic acid residue of which lies in position 3 or 11 in the form of cyclized pyroglutamate. Four oligopeptides were identified using mirror image phage display technology.

First claim

The invention claimed is:

1. A D-enantiomeric peptide, comprising a sequence selected from the group consisting of: SEQ ID NO:1, 2, 3, 4 and a mixture thereof:
wherein said D-enantiomeric peptide, at a sequence portion consisting of one of said SEQ ID NO: 1, 2, 3, and 4 binds to amino-terminal truncated amyloid-beta peptide; and
wherein said amino-terminal truncated amyloid-beta peptide is a species of amino-terminal truncated amyloid-beta peptide having a free glutamic acid residue in position 3 in the form of cyclized pyroglutamate.

2. The D-enantiomeric peptide according to claim 1 , wherein the sequence is comprised of D-enantiomeric amino acids.

3. The D-enantiomeric peptide according to claim 2 , wherein the D-enantiomeric peptide is comprised of at least 60% D-enantiomeric amino acids.

4. The D-enantiomeric peptide according to claim 1 , for use in medicine.

5. The D-enantiomeric peptide according to claim 1 , for treatment of Alzheimer's disease.

6. A therapeutic agent for treating Alzheimer's disease comprising the D-enantiomeric peptide according to claim 1 .

7. The therapeutic agent according to claim 6 , wherein the D-enantiomeric peptide is comprised of D-enantiomeric amino acids.

8. A D-enantiomeric peptide comprising a sequence selected from the group consisting of SEQ ID NO:1, 2, 3, 4 and a mixture thereof.

9. The D-enantiomeric peptide of claim 8 , wherein the peptide consists of a sequence selected from the group consisting of SEQ ID NO:1, 2, 3, 4 and a mixture thereof.

10. A therapeutic agent for treating Alzheimer's disease comprised of the D-enantiomeric peptide according to claim 8 .

11. The D-enantiomeric peptide according to claim 8 , wherein the D-enantiomeric peptide is comprised of at least 60% D-enantiomeric amino acids.

12. A probe comprising a D-enantiomeric peptide according to claim 1 .

13. A probe comprising a D-enantiomeric peptide according to claim 1 for identifying amyloid-beta oligomers.

14. A probe comprising a D-enantiomeric peptide according to claim 1 for preventing amyloid-beta oligomers.

15. A method for detecting plaques that include amino-terminal truncated amyloid-beta peptides, the free glutamic acid residue of which lies in position 3 in the form of cyclized pyroglutamate, comprising the steps of:
contacting the plaques with a labelled D-enantiomeric peptide or a probe that binds to the amino-terminal truncated amyloid-beta peptide at a portion of the D-enantiomeric peptide consisting of a sequence selected from the group consisting of SEQ ID NO. 1, 2, 3 and 4; and
detecting the plaques by means of an imaging method.

16. The method according to claim 15 , wherein the peptide sequence is comprised of D-enantiomeric amino acids.

Assignees

• Forschungszentrum Juelich Gmbh

Inventors

• Willbold Dieter
• Funke Susanne Aileen
• Cinar Yeliz
• Bartnik Dirk
• Demuth Hans-Ulrich
• Kleinschmidt Martin
• Ludwig Hans-Henning

Classifications

• A61P25/28

  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 title

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• G01N33/6896

  Neurological disorders, e.g. Alzheimer's disease · CPC title

• G01N2333/4709

  Amyloid plaque core protein · CPC title