Compounds capable of killing trypanosoma brucei and their application in the treatment of trypanosomiasis

A compound, trypanosomiasis technology, applied in the field of biopharmaceuticals, can solve the problems of unclear mechanism, poor specificity, and low affinity, and achieve the effect of clear inhibition mechanism, high affinity, and efficient killing of Trypanosoma brucei

Active Publication Date: 2020-05-12
UNIV OF SCI & TECH OF CHINA
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Compound I-BET151 has been used as an inhibitor of acetylated lysine binding domain in the treatment of African trypanosomiasis 2 , but there are disadvantages such as poor specificity, low affinity, and unclear mechanism

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
  • Compounds capable of killing trypanosoma brucei and their application in the treatment of trypanosomiasis
  • Compounds capable of killing trypanosoma brucei and their application in the treatment of trypanosomiasis
  • Compounds capable of killing trypanosoma brucei and their application in the treatment of trypanosomiasis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Compound SGC-CBP30 inhibits the binding of TbBDF5-BD1 to H4K10Ac

[0036] (1) Binding of TbBDF5-BD1 to H4K4Ac and H4K10Ac

[0037] According to literature introduction 3，4 , the inventors synthesized a small peptide library of Trypanosoma brucei histone acetylation, and conducted NMR chemical perturbation experiments 5 Screening found that TbBDF5-BD1 (cloning the expression frame of TbBDF5 expression gene 1-369bp into pET22 vector, using BL21 to express the target protein) combined with H4K4Ac and H4K10Ac small peptides, such as figure 1 . Specifically, TbBDF5-BD1 with a concentration of 0.3M was titrated with different concentrations of small peptides to obtain the TbBDF5-BD1 under different concentration ratio conditions 1 H, 15 N-HSQC, finally the different concentration ratio 1 H, 15 Amino acids with chemical shifts can be observed by N-HSQC overlap. The sequence of the acetylated small peptide is shown below: where the acetylated K is underlined. ...

Embodiment 2

[0052] Example 2 Compound SGC-CBP30 can effectively kill Trypanosoma brucei

[0053] Under the same DMSO concentration conditions, 427 cells were treated with 0, 10, 20, and 30 μM SGC-CBP30, and cell counts were performed every day. SGC-CBP30 at a concentration of 10-30 μM can cause 427 cell growth inhibition and a large number of cell death after 24-72 hours of treatment, see Figure 4 a.

[0054] Compound SGC-CBP30 was diluted according to the concentration gradient (35, 30, 25.6, 12.8, 6.4, 3.2, 1.6, 0.8, 0.4, 0.2, 0.1, 0 micromolar) and added to a 96-well plate, and each well was added with 2 ×10 5 200 μL medium of 1 cell, after continuing to culture for 72 hours, add 20 μL resazurin (22.88 mg / ml) to each well, and detect after 6 hours of incubation. The monitoring data were calculated with OriginPro 8.0 software according to the Boltzmann function. Finally, the half-inhibitory concentration (IC50) of SGC-CBP30 obtained by resazurin staining method was 1.370 μM, see ...

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 relates to a compound capable of killing trypanosoma brucei and application of the compound in treating trypanosomosis. The compound is SGC-CBP30, which has a specific target TbBDF5, especially a first acetylated lysine binding domain, and the affinity of the first acetylated lysine binding domain (BD1) of the TbBDF5 is high, so that the trypanosoma brucei is high-efficiently killed.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and relates to a compound capable of killing trypanosome brucei, a pharmaceutical composition containing the compound, and an application thereof in the preparation of a medicament for treating trypanosomiasis. The compound of the present invention can be developed as a precursor molecule of a drug for treating African trypanosomiasis or can be directly used for the treatment of trypanosomiasis. Background technique [0002] Trypanosoma brucei is a single-celled eukaryotic parasite, including three subspecies of Trypanosoma brucei, Trypanosoma brucei gambiae, and Trypanosoma brucei Rhodesia, which can infect humans through the vector tsetse fly And other animals, causing human sleeping sickness (sleeping sickness) and animal Nagana disease (nagana disease), collectively referred to as African trypanosomiasis. Human infection with Trypanosoma brucei has a high mortality rate in the lat...

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 Patents(China)
IPC IPC(8): A61K31/5377A61P33/02
CPCA61K31/5377
Inventor 杨晓廖善晖涂晓明
Owner UNIV OF SCI & TECH OF CHINA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap