Application of compound Ochrephilone in preparing anti-tuberculosis medicine

A tuberculosis and drug technology, applied in the field of biology, can solve the problem of lack of effective anti-tuberculosis drugs and achieve the effect of inhibiting activity

Inactive Publication Date: 2014-04-23
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The purpose of the present invention is to provide an application of a compound in the preparation of

Method used

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  • Application of compound Ochrephilone in preparing anti-tuberculosis medicine
  • Application of compound Ochrephilone in preparing anti-tuberculosis medicine
  • Application of compound Ochrephilone in preparing anti-tuberculosis medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] Example 1 Fusion expression and purification of Mycobacterium tuberculosis serine / threonine protein kinase G protein.

[0073] S1. The gene cloning of Mycobacterium tuberculosis serine / threonine protein kinase G was carried out according to the following steps: Genomic DNA of Mycobacterium tuberculosis H37Rv was extracted by phenol-chloroform extraction method, and according to the known Mycobacterium tuberculosis serine / threonine protein Kinase G gene sequence was designed and primers were synthesized, NdeI and XhoI restriction sites were added to the 5' ends of the upstream and downstream primers respectively, the pkng gene was cloned by PCR, and detected by 1.0% agarose gel electrophoresis, 2253 base pair long DNA fragment of Mycobacterium tuberculosis serine / threonine protein kinase G (see figure 1 ). Recover by electrophoresis (the kit for recovering DNA fragments from agarose gel is a product of Omega Company), purify the amplified gene fragments, dissolve them i...

Embodiment 2

[0081] Example 2 Analysis of the Inhibitory Enzyme Activity of Compound Ochrephilone on Mycobacterium tuberculosis Serine / Threonine Protein Kinase G

[0082] The ADP high-throughput kinase detection kit ADP-Glo® Kinase Assay Kit (product of Promega Company) was used to analyze the enzymatic activity of compounds inhibiting Mycobacterium tuberculosis serine / threonine protein kinase G, and the used Mycobacterium tuberculosis serine / threonine The amino acid protein kinase G is the recombinant Mycobacterium tuberculosis serine / threonine protein kinase G fusion protein obtained in Example 1. Add a certain amount of pure ATP, kinase reaction solution, recombinant mycobacterium tuberculosis serine / threonine protein kinase G in the 200ul PCR tube, incubate at room temperature for 20min, and prepare positive control, negative control and blank control wells at the same time, this embodiment The positive control used to inhibit the activity of Mycobacterium tuberculosis serine / threonine...

Embodiment 3

[0086] Example 3 Molecular docking software predictive analysis of the interaction between Ochrephilone and Mycobacterium tuberculosis serine / threonine protein kinase G

[0087] Using the SYBYL X molecular docking software, the protomol was used to represent the binding pocket of the protein. Use three kinds of probes to fill the surface properties of the probe binding pocket, and then carry out structural similarity matching, complementarity, interaction, H-bond acceptor and donor interaction between the small molecule ligand and the probe in the binding pocket during docking, Hydrophobic Interaction Domain Interaction, mimicking the interaction of Ochrephilone with Mycobacterium tuberculosis serine / threonine protein kinase G (see Figure 11 ), the score given by the software is 4.97, and generally a score greater than 4 indicates that there is an interaction, and the reliability is very high.

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Abstract

The invention belongs to the field of biology, and in particular relates to application of a compound Ochrephilone in preparing an anti-tuberculosis medicine. The compound Ochrephilone belongs to the family of natural toxins. Researches discover than the compound Ochrephilone has autophosphorylation activity of mycobacterium tuberculosis serine/serine-threonine kinase G, so that the Ochrephilone can be used for preparing a new anti-tuberculosis medicine by using mycobacterium tuberculosis serine/serine-threonine kinase G as a target.

Description

technical field [0001] The invention belongs to the field of biology, and in particular relates to the application of compound Ochrephilone in the preparation of anti-tuberculosis drugs. Background technique [0002] Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. According to the latest data collected by the World Health Organization from 204 countries, tuberculosis is still a major infectious disease killer currently threatening human beings. The 2012 Global Tuberculosis Control Report pointed out that in 2011, there were 8.7 million new tuberculosis patients worldwide, and 1.4 million people died of tuberculosis worldwide. In China, the number of people infected by Mycobacterium tuberculosis even exceeds 550 million. If effective control measures are not taken, nearly 50 million infected people in my country may develop tuberculosis in the next 10 years. At present, there are few effective drugs for clinical treatment of tuberculosis, l...

Claims

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Application Information

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IPC IPC(8): A61K31/365A61P31/06
Inventor 陆勇军马双双佘志刚李翰祥牛长红何磊
Owner SUN YAT SEN UNIV
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