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Oxidized a beta peptide

Foreign code F190009713
File No. E112P03US2
Posted date Jan 24, 2019
Country United States of America
Application number 201816018447
Gazette No. 20180312558
Date of filing Jun 26, 2018
Gazette Date Nov 1, 2018
International application number JP2014065749
International publication number WO2014200091
Date of international filing Jun 13, 2014
Date of international publication Dec 18, 2014
Priority data
  • P2013-125797 (Jun 14, 2013) JP
  • P2013-239622 (Nov 20, 2013) JP
  • 2014JP65749 (Jun 13, 2014) WO
  • 201514898409 (Dec 14, 2015) US
Title Oxidized a beta peptide
Abstract The invention provides an Aβ peptide aggregation inhibitor, an Aβ peptide toxicity reducing agent, and a preventive and/or therapeutic agent for Alzheimer's disease.The oxidized Aβ peptide in which one or more amino acid residues of Aβ peptide have been oxidized (excluding an oxidized Aβ peptide in which only Met has been oxidized).
Outline of related art and contending technology BACKGROUND ART
Alzheimer's disease is a neurodegenerative disease having pathological characteristics of degeneration and loss of nerve cells, senile plaque formation, and neurofibrillary tangle.Alzheimer's disease induces a cognitive impairment that a memory, recognition, thinking, judgment, and the like are lost progressively, and finally leads to death.
The main substance of the senile plaque deposited in the brain is amyloid β peptide (Aβ peptide) composed of 39 to 43 amino acids.Aβ peptide shows cytotoxicity, and this is considered to induce Alzheimer's disease (Non-Patent Document 1).Aβ peptide secreted from cells is a polypeptide mainly composed of 40 or 42 amino acids.It is known that, among other Aβ peptides, an Aβ peptide composed of 42 amino acids is aggregated strongly, is deposited in the brain early, and has strong cytotoxicity (Non-Patent Document 2).Accordingly, a medical agent for inhibiting production of Aβ peptide and a medical agent for inhibiting aggregation of Aβ peptide are expected to be useful as a preventive and/or therapeutic agent for Alzheimer's disease.
Concerning a medical agent that inhibits production of Aβ peptide, studies have been focused on a substance capable of inhibiting β-secretase and γ-secretase, which are enzymes involved in production of Aβ peptide.In addition, an Aβ peptide degrading enzyme promoter, an anti-Aβ peptide antibody, a medical agent that inhibits aggregation of Aβ peptide, or the like have also been studied.
On the other hand, there have been reported that a Met-oxidized Aβ peptide (i.e., an oxidized product of Aβ peptide in which the sulfur atom of the Met residue has been oxidized) is present in a low amount in the living body, and the Met-oxidized product has lower aggregation than Aβ peptide (Non-Patent Documents 3 to 5).
Scope of claims [claim1]
1. A method of producing an oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized), the method comprising oxidizing an Aβ peptide.
[claim2]
2. The method according to claim 1, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized.
[claim3]
3. The method according to claim 1, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct.
[claim4]
4. The method according to claim 1, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
[claim5]
5. A method of inhibiting aggregation of an Aβ peptide, the method comprising administering the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized).
[claim6]
6. The method according to claim 5, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized.
[claim7]
7. The method according to claim 5, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct.
[claim8]
8. The method according to claim 5, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
[claim9]
9. A method of reducing toxicity of an Aβ peptide, the method comprising administering the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized).
[claim10]
10. The method according to claim 9, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized.
[claim11]
11. The method according to claim 9, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct.
[claim12]
12. The method according to claim 9, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
[claim13]
13. A method of preventing and/or treating Alzheimer's disease, the method comprising administering the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized).
[claim14]
14. The method according to claim 13, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized.
[claim15]
15. The method according to claim 13, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct.
[claim16]
16. The method according to claim 13, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
[claim17]
17. A method of inhibiting aggregation of an Aβ peptide, the method comprising oxidizing an Aβ peptide to the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized).
[claim18]
18. The method according to claim 17, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct.
[claim19]
19. The method according to claim 17, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
[claim20]
20. A method of reducing toxicity of an Aβ peptide, the method comprising oxidizing an Aβ peptide to the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized).
[claim21]
21. The method according to claim 20, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct.
[claim22]
22. The method according to claim 20, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
[claim23]
23. A method of preventing and/or treating Alzheimer's disease, the method comprising oxidizing an Aβ peptide to the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized).
[claim24]
24. The method according to claim 23, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct.
[claim25]
25. The method according to claim 23, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
  • Inventor, and Inventor/Applicant
  • Kanai Motomu
  • Soma Yohei
  • Taniguchi Atsuhiko
  • Sasaki Daisuke
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
IPC(International Patent Classification)
Reference ( R and D project ) ERATO KANAI Life Science Catalysis AREA
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