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A kind of oligopeptide and its derivative and application

A technology of derivatives and oligopeptides, applied in the fields of oligopeptides and their derivatives and applications, can solve the problems of large molecular weight and difficult synthesis, and achieve the effect of small molecular weight, easy synthesis, and inhibition of influenza virus activity

Active Publication Date: 2022-05-20
NANJING ANJI BIOLOGICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Aiming at the problem that the existing anti-influenza virus peptides have relatively large molecular weight and are difficult to synthesize, the present invention provides an oligopeptide and its derivatives and applications. The number of amino acids of this type of polypeptide is less than 7, the molecular weight is small, easy to synthesize and has Inhibits the activity of influenza virus and can specifically bind to the hemagglutinin site, suggesting that it has important development and application value in anti-influenza virus therapy

Method used

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  • A kind of oligopeptide and its derivative and application
  • A kind of oligopeptide and its derivative and application
  • A kind of oligopeptide and its derivative and application

Examples

Experimental program
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Effect test

Embodiment 1

[0035] Virus virulence assay (TCID 50 )

[0036] Influenza H1N1 (FM1), H3N2 (N3), H5N1 and H7N9 virus antigens used in the present invention are virus inactivated antigens with hemagglutination activity, all can cause disease, H1N1, H3N2 are human influenza, H5N1 and H7N9 It is bird flu. Taking H7N9 as an example, the virus virulence was tested to prove its activity. The specific experimental steps and results are as follows:

[0037] After the MDCK cells (influenza virus susceptible canine kidney passage cell strain) in the logarithmic growth phase are laid on a single layer, the influenza virus H1N1 is continuously diluted by 10 times, and 10 -2 ~10 -10 The diluted virus was inoculated into MDCK cells, adsorbed at 37°C for 1 hour, washed twice with PBS, and then replaced with maintenance medium to continue culturing. Normal cells were used as controls, and each well had 4 replicate wells. Observe the cell lesion under an inverted microscope every day, record the lesion de...

Embodiment 2

[0045]The present invention uses the protein database (Protein Data Bank) hemagglutinin protein (1HGG) crystal structure as the research basis, screens out a series of oligopeptides with antiviral activity, its sequence contains W-Arg-Pro-X-Y-Z domain, A class of oligopeptide derivatives is obtained by modifying the short peptide W-Arg-Pro-X-Y-Z with stearic acid. The general structural formula of this kind of oligopeptide derivatives is C 17 h 35 CO-W-Arg-Pro-X-Y-Z, wherein, W is a deletion or a hydrophobic amino acid (such as W is a deletion or Ala); X and Z are hydrophobic amino acids (such as X is Leu, Phe; Z is Ala, Leu ); Y is a positively charged amino acid (for example, Y is Lys, Arg). These oligopeptide derivatives all have antiviral activity and are expected to be developed into ideal antiviral drugs. The specific structure of oligopeptide derivatives can be:

[0046] Oligopeptide I, C 17 h 35 CO-Arg-Pro-Leu-Lys-Ala; or

[0047] Oligopeptide II, C 17 h 35 CO...

Embodiment 3

[0056] Anti-influenza virus efficacy test method:

[0057] Take cells in good logarithmic growth phase, add 0.25% trypsin digestion solution, blow evenly after digestion and fall off, count, and press 2×10 5 cells / well, seeded in 96-well cell culture plate, placed in constant temperature CO 2 Cultivate in the incubator for 16-24h. Set up normal cell control group, virus infection group, positive drug control group and test drug group respectively. Discard the culture medium, wash three times with PBS, add 100TCID to each well except the normal control group 50 Infectious amount of influenza virus, placed in constant temperature CO 2 The incubator was left to rest for 1 hour, unadsorbed virus was discarded, washed twice with PBS, and then drug-containing maintenance solutions with different concentrations were added. There were 6 doses in the test drug group, each with 3 replicate wells. Then continue to cultivate the cell culture plate with the above-mentioned scheme at 3...

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Abstract

The invention discloses an oligopeptide, its derivatives and applications, and belongs to the technical field of biomedicine. The oligopeptide of the present invention contains a -W-Arg-Pro-X-Y-Z domain, and the general structural formula of its derivatives is C 17 h 35 CO-W-Arg-Pro-X-Y-Z, wherein, W is a deletion or a hydrophobic amino acid (such as W is a deletion or Ala); X and Z are hydrophobic amino acids (such as X is Leu, Phe; Z Ala, Leu); Y is a positively charged amino acid (such as Y is Lys, Arg), the experimental results show that this type of polypeptide can significantly inhibit the proliferation of anti-influenza virus, suggesting that it has an important development in the treatment of anti-influenza virus and application value, so it can be used to prepare anti-influenza drugs.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and more specifically relates to an oligopeptide and its derivatives and applications. Background technique [0002] Influenza, as an acute respiratory infectious disease that seriously endangers human health, causes about 500 million people to become sick each year, of which 250,000 to 500,000 people die, and the annual incidence rate in my country is about 10% to 30%. What is even more worrying is that in recent years, human infection with highly pathogenic influenza is an acute respiratory infectious disease that seriously endangers human health. About 10%-30%. What is even more worrying is that in recent years, the number of human infections with highly pathogenic and fatal influenza virus H5N1 and H1N1 subtypes has been increasing, and the mortality rate is quite high. One of the main reasons for the raging influenza virus is its strong ability to mutate antigens, which makes the immun...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06A61K38/08A61P31/16
CPCC07K7/06A61P31/16A61K38/00Y02A50/30
Inventor 徐寒梅牛淼淼
Owner NANJING ANJI BIOLOGICAL TECH CO LTD
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