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Polypeptide, uses thereof in preparation of drugs, and drugs

A technology of drugs and peptides, applied in the field of medicine, can solve problems that need to be studied

Active Publication Date: 2020-04-10
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] However, substances that can inhibit the signaling pathway mediated by K-Ras4B are still to be studied

Method used

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  • Polypeptide, uses thereof in preparation of drugs, and drugs
  • Polypeptide, uses thereof in preparation of drugs, and drugs
  • Polypeptide, uses thereof in preparation of drugs, and drugs

Examples

Experimental program
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Embodiment 1

[0061] The preparation of embodiment 1 compound

[0062] The first amino acid Fmoc-Cys-OMe for solid-phase synthesis can be obtained by purifying the commercially purchased amino acid Fmoc-Cys(Trt)-OH through a two-step reaction, and combined with 2-Cl Chlorotrityl resin for solid-phase synthesis Linked under the action of organic base DIPEA (see literature Diaz-Rodriguez V., et al., Synthesis of Peptides Containing C-Terminal Methyl Esters Using Trityl Side-Chain Anchoring: Application to the Synthesis of a-Factor and a-Factor Analogs. OrganicLetters,2012,14(22),5648-5651.), and obtain the desired polypeptide sequence by Fmoc solid-phase synthesis method, next, use TFA / thioanisole / H 2 The mixed reagent of O / phenol / 1,2-ethanedithiol (82.5 / 5 / 5 / 5 / 2.5, v / v) cuts the polypeptide from the resin and removes the protecting groups of all amino acids, and precipitates in ether After obtaining the crude peptide, dissolve the obtained crude peptide in DMF / BuOH / H 2 O (2 / 1 / 1, v / v), after...

Embodiment 2

[0067] Example 2 Experiment of farnesylated anticancer polypeptide regulating K-Ras4B localization

[0068] 1. Construction and related characterization of cell lines stably expressing mCitrine fluorescent protein-tagged K-Ras4B protein

[0069]The plasmid carrying the mCitrine-K-Ras4B gene was transfected into the MDCK cell line with a transfection reagent (lipofectamine 2000, purchased from Thermo Company), and monoclonal cells were obtained by sorting by flow cytometry, and an appropriate cell line was selected for Expand the culture to obtain a cell line stably expressing fluorescent protein-tagged K-Ras4B protein. The above cell lines were inoculated into a 6-well plate with coverslips (seeding density 100%), and the prepared farnesylated anti-cancer polypeptide Memrasin was added to the serum-containing medium to prepare a final concentration of 0.5 , 10, 20, 40, 60, 80μM solution, then add the corresponding cells, incubate at 37°C for 10 minutes, suck out the working s...

Embodiment 3

[0074] Example 3 Mechanism experiment of farnesylated anti-cancer polypeptide changing K-Ras4B localization

[0075] 1. Intracellular localization of farnesylated anticancer peptides

[0076] A fluorescein-labeled FAM-Memrasin polypeptide was synthesized to observe the localization of farnesylated anti-cancer polypeptides in cells. The polypeptide sequence is H-GLFDIIKKIAESF-K(FAM)K 5 SMTKC(Far)-OMe. Inoculate A549 cells into a 6-well plate with coverslips and dissolve the FAM-Memrasin polypeptide in the cell culture medium to prepare a working solution with a final concentration of 1 μM and add it to the cells, incubate at 37°C for 10 minutes and wash with phosphate buffered saline After the cells were fixed and sealed, the localization of the fluorescent polypeptide in the cells was observed under a confocal microscope. The results were as follows: Figure 4 a. The results show that the fluorescently labeled Memrasin polypeptide has a clear localization on the cell membra...

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Abstract

The invention provides a polypeptide, uses thereof in preparation of drugs, and drugs. The polypeptide comprises a first peptide fragment and a second peptide fragment; and the N end of the first peptide fragment is connected to the C end of the second peptide fragment. The first peptide fragment is selected from an amino acid sequence which has at least 70% of homology with the first 5-20 amino acids of the C end of the amino acid sequence shown in SEQ ID NO: 1; and the second peptide fragment is suitable for aggregating the polypeptide on the surface of a cell membrane. The polypeptide disclosed by the invention can be competitively combined with a binding site on a cell membrane together with K-Ras4B protein to change positioning of K-Ras4B protein in cells and inhibit a K-Ras4B protein-mediated downstream signal pathway; and thus proliferation or growth of cancer cells is inhibited to treat the cancer. The polypeptide has important scientific research and clinical application values.

Description

technical field [0001] The present invention relates to the field of medicine. Specifically, the present invention relates to polypeptides and their use in the preparation of medicines and medicines. Background technique [0002] K-Ras4B protein is the most important subtype of cancer-related protein Ras protein. It must be combined with the inner side of the cell membrane to exert its corresponding function. The inhibition of K-Ras4B-mediated signaling pathway plays an important role in the treatment of cancer. [0003] However, substances that can inhibit the signaling pathway mediated by K-Ras4B are still to be studied. Contents of the invention [0004] The present invention aims to solve at least one of the technical problems existing in the prior art at least to a certain extent. [0005] In one aspect of the invention, the invention provides a polypeptide. According to an embodiment of the present invention, the polypeptide includes: a first peptide segment and a...

Claims

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Application Information

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IPC IPC(8): C07K14/00A61K38/16A61P35/00
CPCA61K38/00A61P35/00C07K14/00
Inventor 陈永湘李方翊李艳梅
Owner TSINGHUA UNIV
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