Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Selective TNFR1 antagonist peptide SN10 and application thereof in rheumatoid arthritis

A rheumatoid, PEG-SN10 technology, applied in the field of biomedicine, can solve the problems of difficult to achieve effective therapeutic effect, small relative molecular mass, short plasma half-life, etc.

Active Publication Date: 2017-08-25
GUILIN EIGHT PLUS ONE PHARMA CO LTD
View PDF7 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, simple small molecule polypeptides have a small relative molecular weight, are easily filtered by the glomerulus and degraded by related proteases in the body, have poor stability, and have a short plasma half-life. therapeutic effect, which to some extent restricts its development and application

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Selective TNFR1 antagonist peptide SN10 and application thereof in rheumatoid arthritis
  • Selective TNFR1 antagonist peptide SN10 and application thereof in rheumatoid arthritis
  • Selective TNFR1 antagonist peptide SN10 and application thereof in rheumatoid arthritis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1: Synthesis of Qinghuan sea snake selective TNFR1 antagonistic peptide Hydrostatin-SN10

[0042] Hydrostatin-SN10 was synthesized by solid-phase peptide synthesis technology, and analyzed by HPLC ( figure 1 ) and MS ( figure 2 ) to analyze its purity and molecular weight, the result shows that its purity>97%, molecular weight is 1250.29g / mol.

Embodiment 2

[0043] Example 2: BIAcore analysis of the binding ability of Hydrostatin-SN10 to TNFR1.

[0044] 1. The running buffer flows through the channel set in the CM-5 sensor chip at a flow rate of 10 μl / min until it reaches the baseline level.

[0045] 2. Use the buffer recommended by the instrument to activate the surface reactive groups on each channel of the chip.

[0046] 3. Dissolve the freeze-dried powder of TNFR1 and TNFR2 with EP buffer, inject samples at a certain concentration to coat the surface of the chip, and then seal the chip with 1mol / L ethanolamine. Before determining the kinetic curve, the regeneration conditions should be tested to select the appropriate regeneration conditions.

[0047] 4. When the running buffer runs to a stable baseline, inject a series of peptides at a concentration, repeat the injection of a peptide at an intermediate concentration, and record the response value of each concentration.

[0048] Such as image 3 As shown, Hydrostatin-SN10 c...

Embodiment 3

[0049] Example 3: MST analysis of the binding ability of Hydrostatin-SN10 and TNFR1.

[0050] 1. Interaction between Hydrostatin-SN10 and TNF-α, TNFR1, TNFR2:

[0051] Prepare a series of gradient concentrations of Hydrostatin-SN10 at a dilution ratio of 1:1, mix equal volumes of fluorescently labeled TNF-α / TNFR1 / TNFR2 200nM with Hydrostatin-SN10 and incubate for 30 minutes in the dark, then use a capillary pipette to draw an appropriate amount of sample on the machine Detect, observe the time trajectory of the relative fluorescence value and the dose-response curve of thermophoresis, and calculate the affinity K by fitting the software NTAffinityAnalysis v2.0.2 D value to determine whether there is a specific binding trend.

[0052] 2. Competitive inhibitory effect of Hydrostatin-SN10 on the combination of TNF-α and TNFR1 / TNFR2:

[0053] Prepare a series of gradient concentrations of TNF-α at a dilution ratio of 1:1, uniformly mix equal volumes of fluorescently labeled TNFR...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
molecular weightaaaaaaaaaa
Login to View More

Abstract

The invention relates to the field of biological medicine, and particularly provides a selective TNFR1 antagonist peptide Hydrostatin-SN10 derived from snake venom of hydrophis cyanocinctus. The selective TNFR1 antagonist peptide Hydrostatin-SN10 has an amino acid sequence shown in an SEQ ID NO:2. The invention further provides a selective TNFR1 antagonist peptide PEG-SN10 based on mPEG-2000 modification. Selective modification is achieved through covalent linkages between a carboxyl group of mPEG-2000 and a free amino group of aspartic acid at a N-terminal of a peptide chain Hydrostatin-SN10. Meanwhile, application of the selective TNFR1 antagonist peptides Hydrostatin-SN10 and PEG-SN10 in preventing and treating rheumatoid arthritis is provided.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a selective TNFR1 antagonistic peptide Hydrostatin-SN10 derived from the venom of Qinghuan sea snake and its application in rheumatoid arthritis. Background technique [0002] Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint synovitis. The main clinical manifestations are joint swelling and pain caused by the synovial membrane of the facet joints. Inflammation and hyperplasia of the synovial membrane lead to erosion of cartilage and bone, narrowing of the joint space, and severe bone destruction and absorption in the late stage lead to joint stiffness, deformity, and dysfunction. In the United States, RA is considered one of the five major diseases (cardiovascular disease, Alzheimer's disease, cancer, AIDS, rheumatoid arthritis) that affect human health. RA can occur at any age, most commonly in the 20-50 age group. About 0.24% of the people ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/46C12N15/12A61K38/17A61K47/60A61P19/02A61P29/00
CPCC07K14/46A61K38/00A61K38/17A61P19/02A61P37/06A61K38/08
Inventor 陆一鸣王洁李安江海龙卞莹莹张川
Owner GUILIN EIGHT PLUS ONE PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com