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

Small molecule compound for inhibiting aggregation of amyloid beta protein as well as preparation method and application of small molecule compound

A technology of small molecule compounds and β proteins, applied in the field of biomedicine, can solve problems such as poor biocompatibility, large molecular weight, and self-aggregation of polypeptides, and achieve the effects of prolonging life, removing movement disorders, and inhibiting aggregation

Pending Publication Date: 2021-11-09
TIANJIN UNIV
View PDF6 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Peptide inhibitors have high specificity and are easy to modify, but peptides are prone to self-aggregation, and the effective concentration is relatively high (ACSchemical neuroscience, 2019, 10:1390-1401)
Protein inhibitors have good biocompatibility and are easy to chemically modify, but have a large molecular weight and poor blood-brain barrier penetration (Journal of inorganic biochemistry, 2017, 171:67-75)
Nano-inhibitors have a large specific surface area and are easy to modify the surface, but have poor biocompatibility and low specificity (ACS applied materials & interfaces, 2015, 7: 5650-5662)

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
  • Small molecule compound for inhibiting aggregation of amyloid beta protein as well as preparation method and application of small molecule compound
  • Small molecule compound for inhibiting aggregation of amyloid beta protein as well as preparation method and application of small molecule compound
  • Small molecule compound for inhibiting aggregation of amyloid beta protein as well as preparation method and application of small molecule compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1: Different concentrations of CTFBA and Aβ 42 ThT fluorescence intensity of the culture after co-cultivation for 48h.

[0029] Aβ with a purity of 95% 42 Dissolve in hexafluoroisopropanol (hexafiuro-2-isopropanol, HFIP) at a concentration of 1.0 mg / mL, destroy the formed aggregates by ultrasonication in an ice bath for 30 min, let stand at 4°C for 2 h to fully dissolve, and then Centrifuge at 4°C and 16,000 g for 20 minutes, take 75% of the supernatant and place it in a -70°C refrigerator overnight to freeze solid. Finally put into the freeze dryer, the Aβ 42 Freeze-dried into cotton flocs and stored in -20°C refrigerator.

[0030] freeze-dried Aβ 42 Dissolve in 20mM NaOH solution, sonicate in an ice bath for 10min to fully dissolve it, and obtain Aβ with a concentration of 275μM 42 mother liquor. Dilute with 27.5 μM ThT in HEPES buffer (20 mM, pH 7.4, containing 100 mM NaCl) to obtain a final concentration of 25 μM Aβ 42 solution as a control experiment...

Embodiment 2

[0034] Example 2: CTFBA on Aβ 42 Aggregation effect.

[0035] Configure Aβ according to the method of Example 1 42 Stock solution, diluted with HEPES buffer (20 mM, pH 7.4, containing 100 mM NaCl) to obtain a final concentration of 25 μM Aβ 42 solution. Reconstitute Aβ containing 25 μM CTFBA 42 solution, Aβ in solution 42 The final concentration was 25 μM. The above solution was incubated at 37° C. and 150 rpm. After culturing for 48 hours, take 20 μL and drop it on the mica sheet, and let it stand for 10 minutes to fully combine the sample with the mica surface. Then wash slowly 7 times with deionized water to remove the salt ions in the buffer, and let it stand to dry. Observation was performed using the tapping mode of an atomic force microscope (CSPM5500, Yuanyuan). Such as figure 2 Show.

[0036] from figure 2 A can be seen that Aβ 42 Dense fibrous aggregates were formed after 48 hours of culture alone, figure 2 CTFBA and Aβ in B 42 After co-cultivation, ...

Embodiment 3

[0037] Example 3: The effect of CTFBA on the removal of amyloid plaques in Caenorhabditis elegans CL2006.

[0038] First prepare NMG medium, weigh 17g of agar powder, 2.5g of peptone and 3g of sodium chloride into the Erlenmeyer flask, add deionized water to 1L, sterilize at 120°C for 20 minutes, cool to 70°C, and pour Add 25mL of 1M potassium dihydrogen phosphate, 1mL of 1M magnesium sulfate, 1mL of 5mg / mL cholesterol and 1mL of 1M calcium chloride into the Erlenmeyer flask in sequence, shake well, pour into the plate, and dry it for later use.

[0039] Prepare LB liquid medium, weigh 2g of peptone, 1g of yeast powder and 2g of sodium chloride into the conical flask, add deionized water to 200mL, pick Escherichia coli OP50 into the LB liquid medium, at 37°C and 220rpm Placed on a shaker for 12 hours. Apply the cultured OP50 bacteria solution to the NGM medium, drop 200 μL into each plate, and put it upside down in a 4°C refrigerator after the bacteria solution is dried.

[...

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
P valueaaaaaaaaaa
Login to View More

Abstract

The invention relates to a small molecule compound for inhibiting amyloid beta protein aggregation and a preparation method and application of the small molecule compound. The preparation method comprises the following steps: coupling glutamine by using carboxyl on the surface of 3,4,5-trihydroxybenzoic acid to obtain a 4-carbamoyl-2-[(3,4,5-trihydroxyphenyl)formylamino]butyric acid compound. The small molecule compound can effectively inhibit the aggregation of amyloid beta protein in a concentration range of 5-25 [mu] M, reduce the content of a beta folding structure and remove amyloid plaques in an Alzheimer's disease model caenorhabditis elegans CL2006 body, and the service life of the CL2006 is prolonged by one third. Compared with similar small-molecule and heterogeneous polypeptide or protein Alzheimer's disease inhibitors, the polypeptide or protein inhibitor has a remarkable amyloid protein inhibition effect and good blood-brain barrier penetrability; and the aggregation form of A[beta]42 can be changed, and the generation of amyloid protein fibers is inhibited. The compound has a wide application prospect in preparation of medicines for treating Alzheimer's disease.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to a small molecular compound for inhibiting aggregation of amyloid beta protein, a preparation method and an application thereof. Background technique [0002] Alzheimer's disease (AD) is a neurodegenerative disease. In recent years, AD has become a global health problem. With the aging of the world population, the incidence of AD has increased. There are about 50 million people in the world suffering from AD. Triple (Lancet, 2021, 397:1577-1590). The clinical manifestations of AD are the loss of memory and cognitive function, and the main pathological features are the deposition of extracellular senile plaques and intracellular neurofibrillary tangles (Nature, 2014, 515:274-278). Among them, senile plaques are formed by the aggregation of amyloid-β protein (Aβ) in brain tissue. Aβ is produced by the hydrolysis of amyloid-βprecursor protein (APP) by β- and γ-secretase, and Aβ ...

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): C07C235/52C07C231/02A61P25/28
CPCC07C235/52A61P25/28
Inventor 董晓燕许少莹余林玲孙彦
Owner TIANJIN UNIV
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