Ang-(1-7) derivative oligopeptides and methods for using and producing the same

Patent metadata

Field	Value
Publication number	US-9796759-B2
Application number	US-201514801557-A
Country	US
Kind code	B2
Filing date	Jul 16, 2015
Priority date	Jul 21, 2014
Publication date	Oct 24, 2017
Grant date	Oct 24, 2017

Abstract

The present invention provides oligopeptides, in particular, Ang-(1-7) derivatives, and methods for using and producing the same. In one particular embodiment, oligopeptides of the invention have higher blood-brain barrier penetration and/or in vivo half-life compared to the native Ang-(1-7), thereby allowing oligopeptides of the invention to be used in a wide variety of clinical applications including in treatment of cognitive dysfunction and/of impairment.

First claim

What is claimed is:

1. An octapeptide having the formula: A 1 -A 2 -A 3 -A 4 -A 5 -A 6 -A 7 -A 8 (SEQ ID NO: 1) wherein
A 1 is selected from the group consisting of aspartic acid, glutamic acid, alanine, and glycosylated forms thereof;
A 2 is selected from the group consisting of arginine, histidine, lysine, and glycosylated forms thereof;
A 3 is selected from the group consisting of valine, alanine, isoleucine, leucine, and glycosylated forms thereof;
A 4 is selected from the group consisting of tyrosine, phenylalanine, tryptophan, and glycosylated forms thereof;
A 5 is selected from the group consisting of isoleucine, valine, alanine, leucine, and glycosylated forms thereof;
A 6 is selected from the group consisting of histidine, arginine, lysine, and glycosylated forms thereof;
A 7 is selected from the group consisting of proline, glycine, serine, and glycosylated forms thereof; and
A 8 is selected from the group consisting of serine, threonine, hydroxyproline, and glycosylated forms thereof, and
wherein at least one of A1-A8 is glycosylated.

2. The octapeptide of claim 1 , wherein at least one of A 1 -A 8 is glycosylated with a monosaccharide or disaccharide.

3. The octapeptide of claim 2 , wherein at least one of the monosacharides or disaccharides is selected from the group consisting of glucose, galactose, xylose, fucose, rhamnose, lactose, cellobiose, and melibiose.

4. The octapeptide of claim 1 , wherein A 8 is serine or a glycosylated form thereof.

5. The octapeptide of claim 4 , wherein A 8 is a glycosylated serine.

6. The octapeptide of claim 5 , wherein the A 8 serine is glycosylated with glucose or lactose.

7. The octapeptide of claim 1 , wherein A 8 is terminated with an amino group.

8. The octapeptide of claim 7 , wherein A 8 is a serine that is terminated with an amino group.

9. The octapeptide of claim 8 , wherein the octapeptide has the formula of SEQ ID NO: 7.

10. The octapeptide of claim 8 , wherein A 8 is a glycosylated serine that is terminated with an amino group.

11. The octapeptide of claim 10 , wherein the octapeptide has the formula of SEQ ID NO: 8.

12. The octapeptide of claim 10 , wherein the octapeptide has the formula of SEQ ID NO: 9.

13. The octapeptide of claim 1 , wherein the octapeptide comprises at least one D-amino acid.

14. The octapeptide of claim wherein each of A 1 -A 8 is a D-amino acid.

15. The octapeptide of claim 1 , wherein A 1 is alanine.

16. The octapeptide of claim 15 , wherein at least one of A 1 -A 8 is substituted with a monosaccharide or disaccharide.

17. The octapeptide of claim 15 , wherein A 8 is serine or a glycosylated forms thereof.

18. The octapeptide of claim 17 , wherein A 8 is a glycosylated serine.

19. The octapeptide of claim 15 , wherein A 8 is terminated with an amino group.

20. The octapeptide of claim 19 , wherein A 8 is a serine that is terminated with an amino group.

21. The octapeptide of claim 20 , wherein A 8 is a glycosylated serine that is terminated with an amino group.

22. The octapeptide of claim 15 , wherein the octapeptide comprises at least one D-amino acid.

Assignees

• Univ Arizona
• Univ Arizona

Inventors

• Hay Meredith
• Konhilas John
• Polt Robin L
• Jones Evan

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

• C07K9/001

  the peptide sequence having less than 12 amino acids and not being part of a ring structure · CPC title

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• A61K38/085

  Angiotensins · CPC title

• C07K7/14 Primary

  Angiotensins: Related peptides · CPC title