Bifunctional peptide, complex formed of said bifunctional peptide and nucleic acid molecule, and pharmaceutical composition for treating tumors

A bifunctional peptide and nucleic acid molecule technology, applied in the field of biomedicine, can solve the problems of unconsciousness, loss of appetite, and increased side effects

Active Publication Date: 2017-09-01
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there are also research reports that the "cocktail" system composed entirely of chemotherapeutic drugs has the risk of increased side effects, and patients receiving this therapy have a variety of side effects, including: pain, peripheral nerve insensitivity, loss of appetite, Diarrhea and weight loss, etc., which indicates that the development direction of cancer treatment in the future will change from directly killing cancer cells through chemotherapy drugs to combining chemical drugs, gene drugs, molecular biology targeted drugs, natural plant extracts, etc. "Therapy, to control the proliferation of cancer cells and the development of tumors, and even prevent the occurrence of tumors

Method used

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  • Bifunctional peptide, complex formed of said bifunctional peptide and nucleic acid molecule, and pharmaceutical composition for treating tumors
  • Bifunctional peptide, complex formed of said bifunctional peptide and nucleic acid molecule, and pharmaceutical composition for treating tumors
  • Bifunctional peptide, complex formed of said bifunctional peptide and nucleic acid molecule, and pharmaceutical composition for treating tumors

Examples

Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0085] Synthesis of bifunctional peptide AVPIRRRRRRR

[0086] a: Take 1g of 2-chlorotrityl chloride resin (2-chlorotrityl chloride resin) to the peptide synthesis device (Aldrich fritted filter funnel), add dry dimethylformamide (DMF) to soak the resin for half an hour to make it fully Swell, and finally discharge the solvent DMF.

[0087] b: Weigh two equivalents of Fmoc-Arg (pbf)-OH and dissolve it with DMF, then transfer the solution to the polypeptide synthesis device containing the treated resin in the previous step, then add the catalyst diisopropylethylamine (DIEA (M=129.25), >6eq.), let Fmoc-Arg(pbf)-OH interact with the resin for 1.5 hours at room temperature to fully immobilize it on the resin.

[0088] c: wash the resin with DMF.

[0089] d: Methanol blocked active chlorine: Methanol / DMF (volume ratio 1:4) was reacted with 6 equivalents of DIEA for 30-40min. Wash the resin with DMF.

[0090] e: Add 20 mL of 20% piperidine / DMF (V / V) solution to the resin in the p...

preparation Embodiment 2

[0102] AVPIRRRRRRRRC 12 Preparation of / DOX drug-loaded micelles

[0103] AVPIRRRRRRRRC 12 Preparation of:

[0104] Synthesize manually according to the peptide solid-phase synthesis method. The polypeptide chain segments are all extended from the carboxy-terminus to the amino-terminus on 2-chloro-trityl chloride resin, as described below. First, weigh a certain amount of 2-chloro-trityl chloride resin, fully soak and swell with DMF, and then remove the DMF. according to figure 2 In the synthetic method shown, the first amino acid 12-aminododecanoic acid of the peptide chain is immobilized on the resin, and condensation reaction is carried out by adding 4 equivalents of Fmoc-ADDA-OH dissolved in DMF solution, and 6 equivalents of DIEA are added for Catalyze the reaction, absorb hydrochloric acid, react for 2 hours, wash with DMF for several times, then block unreacted active chlorine groups with methanol, and wash with DMF for several times. The Fmoc protecting group on...

preparation Embodiment 3

[0109] Preparation of pharmaceutical composition composed of AVPIRRRRRRR / p53 / DOX

[0110] Measure 5 μL of p53 TE solution (200ng / μL) into a 1.5mL sterile centrifuge tube, add the corresponding AVPIRRRRRRR solution and mix with DNA according to different w / w ratios, and finally add NaCl solution (150mM) to 100μL, After mixing and shaking for 5s, incubate at 37°C for 30min to obtain the AVPIRRRRRRR / p53 complex. Then the complex is blended with a certain amount of NaCl solution of chemotherapy drug DOX.

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Abstract

The invention relates to a bifunctional peptide, which comprises a cancer cell apoptosis peptide and a membrane-penetrating peptide. The present invention also relates to a complex formed by the bifunctional peptide and a nucleic acid molecule and its use in treating tumors. The present invention also relates to a pharmaceutical composition for combating tumors and tumor multidrug resistance, comprising the bifunctional peptide, tumor therapeutic genes and chemotherapeutic drugs, and its use in treating tumors. The bifunctional peptide involved in the present invention can induce cancer cell apoptosis and promote the peptide and its complex to cross the cell membrane. Moreover, the pharmaceutical composition of the present invention combines bifunctional peptides, tumor therapeutic genes and chemotherapeutic drugs, which can not only reduce the dosage of chemotherapeutic drugs and significantly reduce its toxic and side effects on organisms, but also better treat Inhibit the growth of tumor cells and effectively fight against multidrug resistance of tumors.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically, the invention relates to a bifunctional peptide capable of inducing cancer cell apoptosis and promoting the peptide and its complex to cross the cell membrane. At the same time, the present invention also relates to a complex formed by the bifunctional peptide and nucleic acid molecules, a composition comprising the complex and anticancer chemotherapeutic drugs, and their uses. Background technique [0002] Malignant tumors have always threatened human life. According to the report of the World Health Organization, the incidence of cancer is increasing year by year, and it is showing a younger trend. However, in the process of clinical tumor chemotherapy, despite the continuous emergence of new chemotherapy drugs and continuous improvement of chemotherapy regimens, more than 90% of cancer patients still die of different degrees of tumor drug resistance; During chemotherapy, the...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K47/64A61K38/07A61K48/00A61P35/00
Inventor 黄永焯王慧媛
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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