Unlock instant, AI-driven research and patent intelligence for your innovation.

A dual-target chimeric peptide and its application in the preparation of anti-tumor metastasis drugs

An anti-tumor drug and chimeric peptide technology, applied in the field of biomedicine, can solve the problems of significant toxic and side effects, low bioavailability, low anti-tumor metastasis and value-added effects, and achieve good anti-tumor metastasis and strong anti-tumor activity Effect

Active Publication Date: 2019-09-20
SUN YAT SEN UNIV
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In existing reports, inhibitors targeting CXCR4 can achieve targeting of tumor cells, but have no inhibitory effect on other targets in tumor cells, including the NF-kB signaling pathway, and have low anti-tumor metastasis and proliferation effects; and The research on peptide drugs targeting the BF-kB signaling pathway generally has the problem of low bioavailability, and a membrane-penetrating peptide needs to be added. At present, fat-soluble membrane-penetrating peptides are mainly used as guide peptides to enter cells, but these molecules have no tumor targeting sex, the corresponding side effects are significant

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A dual-target chimeric peptide and its application in the preparation of anti-tumor metastasis drugs
  • A dual-target chimeric peptide and its application in the preparation of anti-tumor metastasis drugs
  • A dual-target chimeric peptide and its application in the preparation of anti-tumor metastasis drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Synthesis and Identification of Dual Targeting Chimeric Peptides

[0038] 1. The dual-targeting chimeric peptide having the amino acid sequence shown in SEQ ID NO.1 of the present invention is obtained by Fmoc / tBu solid-phase organic synthesis method. The obtained polypeptide can selectively enter CXCR4+ tumor cells through targeted recognition with chemokine receptor CXCR4, and effectively inhibit the CXCR4+ / SDF-1a functional axis and NF-kB signaling pathway. Therefore, the polypeptide according to the present invention has the effect of targeting tumor cells and inhibiting tumor migration, and can be used in drugs for tumor-targeted therapy, such as in targeted anti-tumor metastasis drug systems.

[0039] In addition, the inventors simultaneously synthesized two other polypeptide molecules, separate VQRKRQKLMP (SEQ ID NO.3) (NF-kB p50 subunit nuclear translocation sequence) and AAVALLPAVLLALLAPVQRKRQKLMPK (SEQ ID NO.4, that is, in SEQ ID NO.3 A fat-soluble ...

Embodiment 2

[0045] Example 2 Dual Targeting Chimeric Peptide Targeted Entry into CXCR4+ Tumor Cells

[0046] 1. Peptide targeting into CXCR4+ tumor cells

[0047] (1) Identification of CXCR4 by flow cytometry + / -expression cell line

[0048] Two kinds of tumor cells A549 and Hela use DMEM medium, non-tumor cells CHO (Chinese hamster ovary cell CHO) use RPMI1640 medium, at 37°C 5% CO 2 cultured in an incubator. When the cells were in good condition, trypsin was added, washed with PBS and counted. Take 2 x 100 μl of each cell (containing 10 6 cells), one of which was added with 5 μl of PE-labeled CXCR4 monoclonal antibody (PE-12G5), and the other was a negative control. Incubate at 4°C in the dark for 30 min, and analyze the number of cell surface receptors by flow cytometry.

[0049] figure 2 Middle panels D and E compared the negative control, showing that tumor cells A549 and Hela cells highly expressed CXCR4 receptors, while non-tumor cells CHO CXCR4 expressed less. The experi...

Embodiment 3

[0058] Example 3 Transwell cell migration inhibition test of lung adenocarcinoma cell A549 and cervical cancer Hela cell

[0059] 1. The migration inhibition experiment of dual-target chimeric peptides on tumor cells

[0060] (1) Material

[0061] The migration inhibition experiment used a migration device consisting of a 12-well polystyrene culture plate and a transwell chamber (Costor 3421 type). The bottom of the upper chamber is covered with a polycarbonate membrane with a diameter of 6.5 mm and a membrane pore size of 5 μm.

[0062] SDF-1α (100 μg / ml, donated by Dr. Ma Weifeng, Laboratory of Molecular Biology, School of Pharmacy, Sun Yat-sen University) was dissolved in sterile deionized water and stored at -20°C.

[0063] Lung adenocarcinoma cells A549 and cervical cancer Hela cells.

[0064] (2) Migration inhibition experiment

[0065] Add 600 μl and 100 μl DMEM culture solution to 12-well cell culture plate and transwell chamber respectively, and store at 37°C, 5% ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
diameteraaaaaaaaaa
pore sizeaaaaaaaaaa
Login to View More

Abstract

The invention discloses a double-targeting chimeric peptide and an application thereof in preparation of an anti-tumor metastasis drug. The chimeric peptide has an amino acid sequence shown in SEQ ID NO.1, acts on CXCR4+ tumor cells in a targeting manner, performs synergistic inhibition of a CXCR4 / SDF-1a functional axis and an NF-kB signaling pathway in the tumor cells, and reduces CXCR4+ tumor cell migration and invasion abilities. Specifically, the chimeric peptide is formed by engomphosis of an SDF-1a N-terminal sequence and a nuclear localization sequence (NLS) of an NF-kB P50 subunit; a tumor cell surface receptor CXCR4 is identified through the N-terminal sequence in a targeting manner, and the intracellular SDF-1a / CXCR4 function axis role is inhibited; and the chimeric peptide also as a membrane penetrating peptide promotes the NF-kB P50 subunit NLS sequence to effectively enter the tumor cells, inhibits NF-kB nuclear import transcription process in a targeting manner, and has important value in study of multi-target antitumor metastasis drugs.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to a dual-target chimeric peptide and its application in the preparation of anti-tumor metastasis drugs. Background technique [0002] Tumor is a serious disease that endangers human health, and its typical feature is uncontrolled proliferation and metastasis. Although in the past few decades, due to the advancement of surgery, radiotherapy and chemotherapy, tumor treatment has made great progress, but multiple organ failure caused by tumor metastasis is still the main cause of tumor death, so highly metastatic tumors are called malignant tumors. Therefore, for new targets and mechanisms of action, the development of drugs that effectively inhibit tumor metastasis is an important direction for improving multi-organ metastasis of malignant tumors in the future, and it is also an important way to change the status quo of tumor treatment as a whole. [0003] A la...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00A61K38/16A61P35/04
Inventor 邵伟艳卜宪章孙海霞刘翠区敬华
Owner SUN YAT SEN UNIV