Cyclic, amyloid beta-binding peptides and the use thereof

Patent metadata

Field	Value
Publication number	US-10428127-B2
Application number	US-201415022712-A
Country	US
Kind code	B2
Filing date	Sep 23, 2014
Priority date	Sep 26, 2013
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

A peptide comprising at least one peptide binding to an amyloid beta species, wherein the peptide includes an amino acid sequence that is present in cyclized form. The use of the peptides in medicine, in particular for treating Alzheimer's disease, is disclosed.

First claim

The invention claimed is:

1. A cyclic peptide comprising:
a linear sequence of amino acids from a first amino acid to a last amino acid for binding to amyloid beta species, wherein the linear sequence comprises one or more sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11;
wherein said linear sequence of amino acids is in a cyclic form in which a first amino acid of the linear sequence has a covalent bond to a last amino acid of the linear sequence either directly or via a linker group comprising biotin or a streptavidin tetramer.

2. The cyclic peptide according to claim 1 , which is substantially composed of D-enantiomeric amino acids.

3. The cyclic peptide according to claim 1 , bound to amyloid beta species at a plurality of binding sites on the cyclic peptide with a dissociation constant (KD value) of no more than 1 μM.

4. The cyclic peptide according to claim 1 , wherein the cyclic peptide comprises the linker group,
wherein said linker group is not part of said linear sequence, and
wherein said linear sequence of amino acids has said cyclic form in which said first amino acid has said covalent bond to said last amino acid via said linker group.

5. The cyclic peptide according to claim 1 , bound to said amyloid beta species, wherein said linear sequence of amino acids comprises a plurality of the sequences selected from the group consisting of SEQ ID NO: 1 SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 each one of said plurality of sequences being bound to said amyloid beta species and said linear sequence remaining in said cyclic form with said covalent bond while bound to said amyloid beta species.

6. The cyclic peptide according to claim 1 , wherein said linear sequence consists of a plurality of identical sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 bonded to each other.

7. The cyclic peptide according to claim 1 , wherein said linear sequence consists of a plurality of sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 covalently bonded to each other.

8. The cyclic peptide according to claim 1 , wherein said linear sequence of amino acids comprises a plurality of sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11.

9. A kit, comprising at least one cyclic peptide according to claim 1 and a container in which the at least one cyclic peptide is packaged.

10. A probe, comprising at least one cyclic peptide according to claim 1 and a material selected from the group consisting of dyes, fluorescent dyes, radioactive isotopes and gadolinium.

11. A method for treating Alzheimer's disease, comprising administering to a person suffering from Alzheimer's disease a composition comprising at least one cyclic peptide according to claim 1 .

12. A method for identifying and quantitatively and/or qualitatively determining amyloid beta species, comprising contacting amyloid beta species with a probe comprising the cyclic peptide of claim 1 .

13. A method for reducing formation of amyloid beta oligomers from amyloid beta species, comprising contacting the amyloid beta species with the cyclic peptide of claim 1 .

14. A method for forming non-toxic polymer-amyloid beta oligomer complexes from amyloid beta species, comprising contacting the amyloid beta species with the cyclic peptide of claim 1 .

15. The cyclic peptide according to claim 1 bound to said beta amyloid species at a first plurality of high-affinity binding sites on the cyclic peptide and bound to said beta amyloid species at a second plurality of low-affinity binding sites on the cyclic peptide,
wherein each high affinity binding site among said first plurality has a dissociation constant (KD value) of no more than 1 μM.

16. The cyclic peptide according to claim 1 , bound to amyloid beta oligomers at a plurality of binding sites on the cyclic peptide with a dissociation constant (KD value) of no more than 100 nM.

17. The cyclic peptide according to claim 1 , bound to amyloid beta fibrils at a plurality of binding sites on the cyclic peptide with a dissociation constant (KD value) of no more than 10 nM.

18. A cyclic peptide comprising:
a linear sequence of amino acids from a first amino acid to a last amino acid for binding to amyloid beta species, wherein the linear sequence comprises one or more sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11; and
wherein said linear sequence of amino acids is in a cyclic form in which a first amino acid of the linear sequence has a covalent bond directly to a last amino acid of the linear sequence.

Assignees

• Forschungszentrum Juelich Gmbh

Inventors

• Willbold Dieter
• Brener Oleksandr

Classifications

• A61K38/00

  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 title

• G01N33/6896

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

• 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

• C07K14/4711 Primary

  Alzheimer's disease; Amyloid plaque core protein · CPC title

• A61K38/12

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title