Ang-(1-7) and derivative oligopeptides for the treatment of traumatic brain injury and other cognitive impairments

Patent metadata

Field	Value
Publication number	US-2018200326-A1
Application number	US-201815865678-A
Country	US
Kind code	A1
Filing date	Jan 9, 2018
Priority date	Jan 9, 2017
Publication date	Jul 19, 2018
Grant date	—

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/or traumatic brain injury.

First claim

What is claimed is:

1 . A method for treating a traumatic brain injury in a subject comprising administering a therapeutically effective amount of an oligopeptide 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 can be present or absent, wherein when A 8 is present, A 8 is selected from the group consisting of serine, threonine, hydroxyproline, and glycosylated forms thereof,

2 . The method of claim 1 , wherein the traumatic brain injury is a concussion.

3 . The method of claim 1 , wherein the traumatic brain injury is a penetrating brain injury.

4 . The method of claim 1 , wherein (a) A 7 is terminated with an amino group and A 8 is absent or (b) A 8 is terminated with an amino group.

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

6 . The method of claim 5 , 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.

7 . The method of claim 5 , wherein (a) A 7 is terminated with an amino group and A 8 is absent or (b) A 8 is terminated with an amino group.

8 . The method of claim 1 , wherein A 8 is glycosylated with a monosaccharide or disaccharide or A 8 is absent and A 7 is glycosylated with a monosaccharide or disaccharide.

9 . The method of claim 8 , 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.

10 . The method of claim 8 , wherein (a) A 7 is terminated with an amino group and A 8 is absent or (b) A 8 is terminated with an amino group.

11 . The method of claim 1 , wherein (a) A 7 is a serine or a glycosylated form thereof and A 8 is absent or (b) A 8 is serine or a glycosylated form thereof.

12 . The method of claim 11 , wherein (a) A 7 is glycosylated with glucose or lactose and A 8 is absent or (b) A 8 is glycosylated with glucose or lactose.

13 . The method of claim 11 , wherein (a) A 7 is terminated with an amino group and A 8 is absent or (b) A 8 is terminated with an amino group.

14 . The method of claim 1 , wherein the oligopeptide is selected from the group consisting of PN-A2, PN-A3, PN-A4, PN-A5, and PN-A6.

15 . The method of claim 14 , wherein the oligopeptide is PN-A5.

16 . The method of claim 14 , wherein the oligopeptide is PN-A6.

17 . The method of claim 1 , wherein the oligopeptide comprises at least one D-amino acid.

18 . The method of claim 1 , wherein each amino acid is a D-amino acid.

Assignees

• Univ Arizona

Inventors

• Hay Meredith
• Polt Robin L
• Vanderah Todd
• Milnes Tally

Classifications

• A61K38/085 Primary

  Angiotensins · CPC title

• A61K38/14

  Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin} · 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