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

MERS-CoV fusion inhibitor

A technology of compounds and mixtures used in the field of biomedicine

Active Publication Date: 2019-08-16
ACADEMY OF MILITARY MEDICAL SCI
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current research on N-peptide fusion inhibitors derived from the NHR region of MERS-CoV is not mature, so it is necessary to develop peptide compounds that can effectively inhibit MERS-CoV fusion

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
  • MERS-CoV fusion inhibitor
  • MERS-CoV fusion inhibitor
  • MERS-CoV fusion inhibitor

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0135] Preparation Example 1. Preparation of Polypeptide Monomer

[0136] Compound 1 (SEQ ID NO:9) was synthesized using a standard Fmoc solid-phase method. Rink Amide resin is selected, and the peptide chain is extended from the C-terminus to the N-terminus. The condensing agent is HBTU / HOBt / DIEA. The deprotecting agent is piperidine / DMF solution. The peptide sequence was synthesized using a CS Bio peptide synthesizer, and finally the N-terminus of the peptide was capped with acetic anhydride reagent. The lysate was trifluoroacetic acid / ethanedithiol / m-cresol (TFA / EDT / m-cresol), and the crude peptide was dissolved in water and then lyophilized for storage. Separation and purification were carried out by medium pressure liquid chromatography or high pressure liquid chromatography (HPLC), the pure peptide content was >95%, and the molecular weight of the peptide sequence was determined by matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS).

[0...

preparation example 2

[0149] Preparation example 2. Preparation of polypeptide trimer

[0150] Compound 2 ((SEQ ID NO:9) 3 ) The synthesis of the monomeric peptide sequence is the same as in Preparation Example 1, but when the resin is attached to the amino acid, the E (12th position calculated from the N-terminal) that requires site modification is replaced by E (OAll, O-allyl). After the sequence is synthesized on the resin, it is not cleaved, and the following further chemical modifications are performed.

[0151] On the resin, remove the side chain protecting group OAlll of E(OAll) in the polypeptide sequence: the synthetic polypeptide resin is transferred into a 50ml eggplant-shaped bottle, and weighs 0.26g tetrakis(triphenylphosphopalladium) (Pd( PPh 3 ) 4 ), 0.31g of 5,5-dimethylcyclohexanedione was dissolved in 8ml of anhydrous tetrahydrofuran and dichloromethane mixed solvent (v / v=1 / 1), added to an eggplant-shaped bottle, and reacted in the dark for 6h. In the polypeptide reactor, wash...

Embodiment 1

[0160] Example 1. Characterization of the α-helicity of polypeptide compounds

[0161] 1. Configuration of N-peptide solution

[0162] Weigh about 1 mg of pure peptide and dissolve in 700 μL ddHO 2 In O, shake and centrifuge, take the supernatant and calibrate the concentration of the N-peptide solution on the nanodrop2000 instrument. Using buffer PBS (pH=7.2) as diluent, prepare 10 μM N-peptide solution, 500 μL.

[0163] 2. Test the helicity of N-peptide solution

[0164] Add the prepared N-peptide solution into the cuvette, measure its helical absorption value (the blank control absorption value has been deducted) in the circular dichroism spectrometer, and convert it into helicity according to the following formula:

[0165]

[0166] Wherein the concentration (c) refers to the concentration value of the N-peptide solution, the path (L) refers to the length of the reference pool, and the number of residues (N) refers to the number of amide bonds for measuring the N-pep...

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

No PUM Login to View More

Abstract

The invention belongs to the field of biomedicine, and relates to a compound shown in a formula I, stereoisomers, mixtures or pharmaceutically-acceptable salts of the compound. The invention further relates to an application of the compound, stereoisomers, mixtures or pharmaceutically-acceptable salts thereof in preparing medicines for treating and / or preventing MERS-CoV infection or diseases related to MERS-CoV infection (such as Middle East respiratory syndrome). The formula is as below:(Z-Ile-Glu-X1-Ile-Val-Lys-Lys-Ile-X2-X3-Ile-Glu-Arg-Ala-Ile-Glu-Ala-Gln-Gln-X4-Leu-Leu-Gln-Leu-Thr-Val-Trp-X5-Ile-Lys-Gln-Leu-Gln-Ala-Arg-Ile-Leu-B)n(I).

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a polypeptide compound against MERS-CoV infection, its stereoisomer, its mixture, or a pharmaceutically acceptable salt thereof. The present invention also relates to the use of the polypeptide compound, its stereoisomer, mixture, or pharmaceutically acceptable salt in the preparation of treatment and / or prevention of MERS-CoV infection or diseases associated with MERS-CoV infection (such as Middle East Respiratory Syndrome ) use in medicine. Background technique [0002] In 2012, a novel coronavirus known as Middle East respiratory syndrome coronavirus (MERS-CoV) was circulating in the Middle East. The virus can cause a SARS-like disease, leading to multi-organ failure and a fatality rate of about 40% in the population. Since MERS-CoV has the ability of human-to-human transmission, there is a possibility of large-scale epidemics in the population. Therefore, it is urgent to conduct in...

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
IPC IPC(8): C07K14/16C07K1/06A61K38/16A61P31/14
CPCA61K38/00A61P31/14C07K14/005C07K19/00C12N2740/16022Y02P20/55
Inventor 王潮李悦
Owner ACADEMY OF MILITARY MEDICAL SCI
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