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Anti-tumor peptide molecule with multiplex targeting performance and selectivity and application thereof

A dual-targeting, anti-tumor technology, applied in anti-tumor drugs, medical preparations containing active ingredients, peptide/protein components, etc., can solve problems such as fever, leukopenia, and susceptibility to infection

Active Publication Date: 2017-10-03
CHINA UNIV OF PETROLEUM (EAST CHINA)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to many shortcomings and toxic side effects of traditional chemotherapy drugs, when killing tumor cells, it will also cause serious damage to normal cells in the human body, resulting in different side effects, such as bone marrow suppression, leukopenia, and patient fatigue. Weakness, decreased resistance, susceptibility to infection, fever, bleeding, etc., greatly reduce the quality of life of patients, and sometimes even have to stop treatment due to serious adverse reactions

Method used

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  • Anti-tumor peptide molecule with multiplex targeting performance and selectivity and application thereof
  • Anti-tumor peptide molecule with multiplex targeting performance and selectivity and application thereof
  • Anti-tumor peptide molecule with multiplex targeting performance and selectivity and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Synthesis of anti-tumor peptide molecules with dual targeting and selectivity (take the synthesis of 0.25mmol peptide molecules as an example)

[0033] 1. Materials

[0034] (1) Weigh 0.982g of MBHA resin with a loading capacity of 0.318mmol / g, and swell in DCM overnight;

[0035] (2) Prepare a DMF (dimethylformamide) solution of the following amino acids at a concentration of 0.2mol / L:

[0036] Fmoc-Ala-OH (N-fluorenylmethoxycarbonyl-alanine): volume 11mL, mass 0.82g;

[0037] Fmoc-Gly-OH (N-fluorenylmethoxycarbonyl-glycine): volume 56mL, mass 1.90g;

[0038] Fmoc-Pro-OH (N-fluorenylmethoxycarbonyl-proline): volume 11mL, mass 0.74g;

[0039] Fmoc-Ile-OH (N-fluorenylmethoxycarbonyl-isoleucine): volume 32mL, mass 2.26g;

[0040] Fmoc-Lys(Boc)-OH(N-fluorenylmethoxycarbonyl-N'-tert-butoxycarbonyl-lysine): volume 32mL, mass 3.00g;

[0041] Fmoc-Arg(Pbf)-OH(N-fluorenylmethoxycarbonyl-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-arginine): volume 84mL, mass 10.92g;...

Embodiment 2

[0054] Cytotoxicity test of anti-tumor polypeptide molecules with dual targeting and selectivity

[0055] First inoculate 100 μL of a sterile 96-well plate at a density of 1×10 5 Cells / mL cells were placed in a 37°C incubator for 24 hours. After they adhered to the wall, the culture solution in the well plate was sucked out, and 100 μL of fresh culture solution and 100 μL of filtered polypeptide solutions of different concentrations were added to each well. Set up 4 parallel Abs for each concentration peptide In addition, the wells that only added Tris (trihydroxymethylaminomethane) buffer and no peptide were used as the control group Abs Tris , and then put the well plate back in the incubator at 37°C for 48h. After the effect was completed, 20 μL of MTT (3-(4,5-dimethylthiazole-2)-2 at a concentration of 5 mg / mL was added to each well. , 5-diphenyltetrazolium bromide) solution, continue culturing in the incubator for 4 hours, then suck out the liquid in the well plate, add...

Embodiment 3

[0059] Enzyme test

[0060] Prepare peptide molecules with pH 7.0 Tris buffer:

[0061] Ac-Arg-Gly-Asp-Gly-Pro-Leu-Gly-Leu-Ala-Gly-Ile-Ile-Ile-Gly-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-NH2 (RR22) solution, the concentration of which is 100 μM, a part of the solution is taken out and added to matrix metalloproteinase MMP7, and the sample is characterized by mass spectrometry.

[0062] The result is as figure 2 as shown, figure 2 The mass spectrum of (a) and figure 2 (b) all show that matrix metalloproteinase MMP7 can successfully enzymatically hydrolyze polypeptide molecules and release amphiphilic

[0063] Leu-Ala-Gly-Ile-Ile-Ile-Gly-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-NH2 (LR15) fragment.

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Abstract

The invention provides an anti-tumor peptide molecule with multiplex targeting performance and selectivity and application thereof, and belongs to the field of targeted medicine molecules. The molecule structure completeness and the cell non-toxicity can be maintained in the normal cell positions; cell antipersonnel fragments can be released in the tumor cell positions, so that the selective killing on the tumor cells can be realized; meanwhile, the duplex targeting performance can be realized on the tumor cells. The peptide molecule has the following sequence of Ac-Arg-Gly-Asp-Gly-Pro-Leu-Gly-Leu-Ala-Gly-Ile-Ile-Ile-Gly-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-NH2(RR22), and can be subjected to enzymolysis by substrate metalloprotease to release LR15 fragments Leu-Ala-Gly-Ile-Ile-Ile-Gly-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-NH2 with the tumor cell killing performance. The anti-tumor peptide molecule provided by the invention can be used for preparing tumor cell selective killing agents, and can be effectively applied to targeted killing of tumor cells. Compared with other targeting medicine, the anti-tumor peptide molecule has wider application values.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the field of targeted drug molecules, in particular to an anti-tumor polypeptide molecule with dual targeting and selectivity and its application. Background technique [0002] Cancer is one of the biggest killers threatening human life worldwide, and cancer treatment is a major challenge facing current medical research. Chemotherapy, surgery, and radiotherapy are listed as the three basic means of cancer treatment, and play an important role in cancer treatment. However, due to many shortcomings and toxic side effects of traditional chemotherapy drugs, when killing tumor cells, it will also cause serious damage to normal cells in the human body, resulting in different side effects, such as bone marrow suppression, leukopenia, and patient fatigue. Weakness, decreased resistance, susceptibility to infection, fever, bleeding, etc., greatly reduce the quality of life of patients, and s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00A61K38/16A61P35/00
Inventor 曹美文赵文婧卢沙徐海
Owner CHINA UNIV OF PETROLEUM (EAST CHINA)
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