Peptide therapeutics for autoimmune and inflammatory diseases

A technology for autoimmune diseases and inflammatory diseases, applied in allergic diseases, anti-inflammatory agents, non-central analgesics, etc.

Pending Publication Date: 2022-05-13
GENESEN CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has been suggested that peptides derived from the N-terminal half of αC plus the CC loop (TR6) inhibit TLR2 / 1 and TLR4 signaling but not the C-terminal half plus the CD loop (TR7)

Method used

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  • Peptide therapeutics for autoimmune and inflammatory diseases
  • Peptide therapeutics for autoimmune and inflammatory diseases
  • Peptide therapeutics for autoimmune and inflammatory diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0090] Example 1: Materials and Methods

Embodiment 1-1

[0091] Example 1-1: Peptide synthesis, reagents and cell line optimization

[0092] Peptides were synthesized by Biostem (Ansan, Korea) with 97.09% (MIP1), 97.17% (MIP2) and 95.1% (MIP3) purities, respectively, as determined by reversed-phase high performance liquid chromatography (HPLC; Shimadzu Prominence). All peptides were detected at 220 nm using a Shiseido Capcell pak C18 column (4.6 mm x 50 mm) with a gradient of 10%-60% acetonitrile in 0.1% trifluoroacetic acid (TFA)-water at a flow rate of 1 mL / min. The molecular weights of MIP1, MIP2 and MIP3 were measured by Shimadzu LCMS-2020 and were 2182.6 Da, 3710.5 Da and 3680.5 Da, respectively. LPS (E. coli 0111:B4) and adenosine triphosphate (ATP) were purchased from Sigma-Aldrich. PAM 3 CSK 4 (TLR1 / 2), Poly(I:C)(TLR3), Imiquimod (IMQ; R837, TLR7), R848 (TLR7 / 8) and CpG-ODN (TLR9) were purchased from Thermo Fisher Scientific, Inc., and FSL-1 (TLR2 / 6) were purchased from InvivoGen (San Diego, CA, USA).

[0093] Put HEK-B...

Embodiment 1-2

[0094] Example 1-2: Cell Viability Assay

[0095] Put HEK-Blue TM hTLR4 cells at 5 × 10 4 Density distribution of cells / well, RAW264.7 cells and THP-1 cells were distributed at 2 × 10 5 Density assignment of cells / well. All cells were grown overnight in 96-well plates (BD Biosciences, San Jose, CA, USA). Cell viability was determined using the colorimetric 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylmethanezan (MTT) assay (Sigma-Aldrich) and / or MTS (3-(4 , 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazole) (Promega Madison, WI, USA) to assay, performed as previously described (Kwon, H.K. et al., Toxicological sciences: an official journal of the Society of Toxicology 148, 204-219 (2015)).

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Abstract

The present invention relates to a peptide that inhibits a Toll-like receptor (TLR) signaling pathway. More specifically, the present invention relates to: a peptide that strongly binds to a TIR-containing molecule to inhibit the TLR, in particular the TLR4 signaling pathway; a fusion peptide in which a cell penetrating peptide is conjugated to the peptide; a TLR4 antagonist comprising the peptide or the fusion peptide; and a composition for preventing or treating an autoimmune disease or an inflammatory disease, the composition comprising the peptide or the fusion peptide. According to the present invention, the peptide has an inhibitory effect on a plurality of TLR signaling pathways including TLR4, blocks a MyD88-dependent TLR4 pathway and a TRIF-dependent TLR4 pathway, and has a significant disease-alleviating effect on rheumatoid arthritis, psoriasis, systemic lupus erythematosus and non-alcoholic steatohepatitis, therefore, the compound can be effectively used as a therapeutic agent for immune-related diseases and inflammatory diseases in which negative regulation of TLR is required.

Description

technical field [0001] The present invention relates to peptides that inhibit the signaling pathway of Toll-like receptors (TLRs), and more particularly, to peptides that strongly bind to TIR-containing molecules to inhibit the signaling pathways of TLRs (especially TLR4) A fusion peptide in which a cell penetrating peptide is combined with the above-mentioned peptide; a TLR antagonist comprising the peptide or the fusion peptide; and a pharmaceutical composition comprising the peptide or the fusion peptide for preventing or treating diseases mediated by the TLR pathway. Background technique [0002] Signaling by Toll-like receptors (TLRs) belonging to the family of pattern recognition receptors is critical for pathogen recognition by the innate immune system. TLRs recognize unique properties presented by pathogens or dead / damaged cells during infection. These features are called Danger-associated molecular patterns (DAMPs) and Pathogen-associated molecular patterns (PAMPs)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08C07K19/00A61K38/10A61K47/64A61P37/02A61P29/00
CPCC07K7/08A61K47/64A61P37/02A61P29/00C07K2319/10A61K38/00C07K14/4713
Inventor 崔相敦徐昌熙金郁玛索德·沙阿阿斯玛·阿切克金己煐郑宰衍金顺善
Owner GENESEN CO LTD
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