Immunity-enhancing peptide analogs and uses thereof

Patent metadata

Field	Value
Publication number	US-2025032573-A1
Application number	US-202418627593-A
Country	US
Kind code	A1
Filing date	Apr 5, 2024
Priority date	Feb 7, 2023
Publication date	Jan 30, 2025
Grant date	—

Abstract

The present invention relates to a WKYMVm peptide analog comprising an amino acid sequence of Trp (W)-Lys (K)-Tyr (Y)-Met (M)-Val (V)-D-Met (m), in which at least one amino acid residue selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence is substituted with a β3-amino acid residue or a peptoid residue, and a use thereof. The WKYMVm peptide analogs of the present invention has effects of increasing stability by increasing in vivo degradation half-life and of promoting activation of innate immune responses by neutrophils through activation of formyl peptide receptors, and thus can be effectively used in preventing or treating a disease that is be prevented or treated by formyl peptide receptors, especially an infectious disease or inflammatory disease.

First claim

What is claimed is:

1 . A WKYMVm peptide analog comprising an amino acid sequence of the following:
Trp (W)-Lys (K)-Tyr (Y)-Met (M)-Val (V)-D-Met (m), wherein at least one amino acid residue selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence is substituted with a β 3 -amino acid residue or a peptoid residue.

2 . The WKYMVm peptide analog of claim 1 , wherein one amino acid residue selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence is substituted with a β 3 -amino acid residue or a peptoid residue.

3 . The WKYMVm peptide analog of claim 1 , wherein two amino acid residues selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence are substituted with a β 3 -amino acid residue or a peptoid residue.

4 . The WKYMVm peptide analog of claim 1 , wherein amino acid residues of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence are substituted with a β 3 -amino acid residue or a peptoid residue.

5 . The WKYMVm peptide analog of claim 1 , wherein the WKYMVm peptide analog in which at least one amino acid residue selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence is substituted with a β 3 -amino acid residue has a following chemical formula:

6 . The WKYMVm peptide analog of claim 1 , wherein the WKYMVm peptide analog in which at least one amino acid residue selected from the group consisting of Lys (K), Tyr (Y), and Met (M) in the amino acid sequence is substituted with a peptoid residue has a following chemical formula:

7 . The WKYMVm peptide analog of claim 1 , wherein the WKYMVm peptide analog induces or promotes activation of a formyl peptide receptor (FPR).

8 . The WKYMVm peptide analog of claim 1 , wherein the WKYMVm peptide analog has one or more characteristics selected from the group consisting of:
(i) promoting activation of innate immune responses by neutrophils; (ii) inducing an increase in calcium ions in neutrophils; (iii) promoting production of reactive oxygen species by neutrophils; (iv) promoting degranulation activity of neutrophils; (v) promoting mobility of neutrophils; and (vi) regulating cytokine production in neutrophils.

9 . The WKYMVm peptide analog of claim 1 , wherein the WKYMVm peptide analog has an increased in vivo degradation half-life compared to a WKYMVm peptide.

10 . A composition comprising a peptide analog of claim 1 .

11 . An immunity-enhancing method comprising administering the composition of claim 10 in a subject in need thereof.

12 . A method of preventing or treating an infectious disease, comprising administering the composition of claim 10 in a subject in need thereof.

13 . The method of claim 12 , wherein the infectious disease is selected from the group consisting of respiratory syncytial (RS) virus infection, keratitis, conjunctivitis, tuberculosis, tuberculous osteomyelitis, tuberculous peritonitis, tuberculous meningitis, cervical lymphadenitis, infectious myositis, fungal infection, acute viral hepatitis, acute gastroenteritis, acute vaginitis, Kikuchi disease, norovirus enteritis, brain abscess, encephalitis, herpes simplex, herpes simplex encephalitis, shingles, Escherichia coli infection, dengue fever, rash, tinea capitis, legionellosis, leptospirosis, listeriosis, malaria, syphilis, melioidosis, viral meningitis, bacterial meningitis, botulism, brucellosis, Vibrio vulnificus sepsis, bacterial shigellosis, Pseudomonas infection, hand, foot-and-mouth disease, amoebic dysentery, lymphadenitis, cervicitis, enterohemorrhagic Escherichia coli infection, sepsis, pulmonary tuberculosis, and staphylococcal infection.

14 . A method of preventing or treating an inflammatory disease, comprising administering the composition of claim 10 in a subject in need thereof.

15 . The method of claim 14 , wherein the inflammatory disease is selected from the group consisting of ankylosing spondylitis, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, arthritis, dermatitis, atopic dermatitis, conjunctivitis, periodontitis, gingivitis, rhinitis, allergic rhinitis, chronic sinusitis, otitis media, pharyngitis, tonsillitis, bronchitis, pneumonia, emphysema, bronchial asthma, pulmonary fibrosis, gastric ulcer, gastritis, Crohn's disease, enteritis, colitis, hemorrhoids, urethritis, gout, rheumatic fever, lupus, fibromyalgia, tendinitis, tenosynovitis, peritendinitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome, multiple sclerosis, ulcers, and wounds.

Assignees

• Research & Business Found Sungkyunkwan Univ
• Univ Yonsei Iacf

Inventors

• Bae Yoe Sik
• Yun Nam Joo
• Cho Hyeon Jin
• Choi Soo Hyuk
• Yoon Hye Rim
• Choi Hee Won
• Seo Eun Jin

Classifications

• C07K7/08

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

• 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

• C07K7/02

  Linear peptides containing at least one abnormal peptide link · CPC title

• A61K38/08 Primary

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61P37/04

  Immunostimulants · CPC title