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Application of Antimicrobial Peptides in Drugs Against Mycobacterial Infection

A technology of Mycobacterium and Mycobacterium smegmatis, applied in the field of pharmacy, can solve the problems of unreported application of antibacterial peptides, the risk of co-infection and the like

Active Publication Date: 2021-09-10
LIAONING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current status of tuberculosis and the main problems: (1) The long-term nature of the treatment plan for drug-sensitive diseases, the first stage of tuberculosis treatment, the first-line anti-tuberculosis drugs isoniazid, rifampicin, pyrazinamide and ethambutol Two months of combined use are required, and the second phase requires combined administration of isoniazid and rifampicin for four months; (2) Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are increasing; ( 3) The rapid increase of HIV-TB co-infection is also a dangerous situation; (4) Latent infection of TB can be up to two years
[0006] But so far, the application of the antimicrobial peptide involved in the present invention in anti-mycobacterial infection has not been reported

Method used

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  • Application of Antimicrobial Peptides in Drugs Against Mycobacterial Infection
  • Application of Antimicrobial Peptides in Drugs Against Mycobacterial Infection
  • Application of Antimicrobial Peptides in Drugs Against Mycobacterial Infection

Examples

Experimental program
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Effect test

Embodiment 1

[0024] The series of antimicrobial peptides of the present invention, P (abbreviation for peptide) is obtained by our laboratory by transforming the antimicrobial peptide chensinin-1 of the Chinese forest frog skin. The antimicrobial peptide is a short peptide with 18 amino acids, and its sequence is: SAVGRHGRRFGLRKHRKH.

[0025] Chensinin-1b is a modified peptide obtained by modifying chensinin-1, replacing the weaker hydrophobic glycine with tryptophan with stronger hydrophobicity and adjusting the amino acid sequence to enhance its amphiphilicity. Its sequence is: SKVWRHWRRFWHRAHRKL.

[0026] The L-P type intercepts the 3-13 amino acids of chensinin-1b, wherein the arginine (R) at the 4th and 10th positions replaces histidine (H) to design the L-P type.

[0027] The D-P type and D / L-P type are obtained by introducing D-arginine into the L sequence.

[0028] C2-D-P type, C4-D-P type, C8-D-P type, C12-D-P type, and C16-D-P type are further improvements to the above-mentione...

Embodiment 2

[0046] 1. The minimum inhibitory concentration experiment of antimicrobial peptides on Mycobacterium smegmatis mc2155 (Mycobacterium Smegmatis)

[0047] (1) Pick a monoclonal colony of Mycobacterium smegmatis and incubate in 7H9 medium containing 10% ADC at 37° C. and 200 rpm for 24 hours. Dilute the cell suspension to OD 600 =10 -3 , about 1×10 6 CFU / mL for use.

[0048] (2) Then prepare a series of concentrations of antibacterial peptides with sterile water, and serially dilute to 100 μM, 50 μM, 25 μM, 12.5 μM, 6.25 μM, 3.13 μM, 1.57 μM.

[0049] (3) Take the 96-well plate and add the plate, add 5 μL of antimicrobial peptide with a final concentration of 100 μM into the 96-well plate, and then add 95 μL with a final concentration of 1×10 6 CFU / mL of Mycobacterium smegmatis, with rifampicin as positive control and water as negative control, after incubation for 48 hours, use a microplate reader to detect bacterial activity at OD600, and calculate according to the absorban...

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Abstract

The invention relates to the field of pharmacy, in particular to the application of antimicrobial peptides in anti-mycobacterium infection drugs. The present invention starts with antimicrobial peptides and develops a series of antimicrobial peptides targeting mycobacteria with special structures and unusual modes of action. The antimicrobial peptides kill bacteria through a membrane destruction mechanism, and bacteria will not develop drug resistance. Antimicrobial peptides, which are the main potential agents for the treatment of tuberculosis, have filled the gap in the absence of new anti-tuberculosis drugs in China for a long time. Therefore, the antimicrobial peptide provided by the present invention can be used to prepare effective drugs against mycobacteria, and is expected to become a potential drug against mycobacterial infection and a main potential drug for treating tuberculosis.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to the application of an antimicrobial peptide in anti-mycobacterium infection drugs. Background technique [0002] Mycobacteria belong to the mycolic acid-containing actinomycetes, and the main characteristic is that the cell wall contains a large amount of lipids, mainly mycolic acids. This is closely related to its dyeability, growth characteristics, pathogenicity, and resistance. Generally, it is not easy to be colored. If it is colored by heating or prolonging the dyeing time, it can resist the decolorization of strong decolorizing agent hydrochloric acid ethanol, so it is also called acid-fast bacilli. The bacterium has no flagella, no spores, and does not produce endotoxins and exotoxins. Its pathogenicity is related to the composition of the bacteria. The diseases caused are all chronic and accompanied by granulomas. There are many types, which can be divided into three categories...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08A61K38/10A61P31/04A61P31/06
CPCA61K38/00A61P31/04A61P31/06C07K7/08
Inventor 董维兵尚德静骆雪月
Owner LIAONING NORMAL UNIVERSITY
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