A kind of polypeptide dip-13 that can antagonize ddx3 protein RNA binding activity and its application

A technology that combines activity and protein, it can be applied to polypeptides, hybrid peptides, and peptide/protein components containing localization/targeting motifs. Effect

Active Publication Date: 2020-03-27
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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  • Description
  • Claims
  • Application Information

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Problems solved by technology

In view of the great potential of DDX3 in the development of tumor-targeted therapeutic drugs, the research team of Johns Hopkins University School of Medicine in the United States developed an inhibitor of DDX3, RK-33, in 2016. This compound can competitively bind to the ATP binding of DDX3 Functional region, and inhibit its RNA binding ability, exhibited significant tumor suppressor function in tumor cells and mouse models; however, due to lack of specificity, this compound cannot meet the needs of tumor targeted therapy

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  • A kind of polypeptide dip-13 that can antagonize ddx3 protein RNA binding activity and its application
  • A kind of polypeptide dip-13 that can antagonize ddx3 protein RNA binding activity and its application
  • A kind of polypeptide dip-13 that can antagonize ddx3 protein RNA binding activity and its application

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Embodiment Construction

[0025] The principles and features of the present invention are described below in conjunction with examples, which are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0026] 1. Synthesis of Antitumor Peptides

[0027] Synthesize an anti-tumor polypeptide by solid-phase synthesis, which includes a tumor cell killing domain and a membrane-penetrating domain, wherein the tumor cell killing domain sequence is shown in SEQ ID NO: 1, and the membrane-penetrating domain sequence is as shown in SEQ ID NO: 1 As shown in ID NO: 2, it is connected to the N-terminal of the tumor cell killing domain, and the obtained sequence is: the amino acid sequence is YGRKKRRQRRR-VLAPTRELAVQIK (SEQ ID NO: 3), and it is named DIP-13. For the convenience of research, we linked FITC labeled with fluorescein isothiocyanate to the C-terminus of the anti-tumor polypeptide, and linked biotin-labeled Biotin to the N-terminus.

[0028] The mechan...

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Abstract

The present invention provides a polypeptide that can antagonize the RNA binding activity of DDX3 protein and its application, and its amino acid sequence is shown in SEQ ID NO: 1; it also relates to an anti-tumor polypeptide and its application, and the anti-tumor polypeptide includes tumor cells The killing domain and the membrane-penetrating domain, the amino acid sequence of the tumor cell killing domain is shown in SEQ ID NO:1. The transmembrane domain of the anti-tumor polypeptide of the present invention has no cytotoxicity itself, but after linking with the tumor cell killing domain, it has obvious effects of inhibiting tumor proliferation, migration and invasion. The anti-tumor polypeptide of the present invention can not only be used as an anti-tumor biotherapeutic drug alone, but is also expected to be combined with other treatment methods to inhibit tumors.

Description

technical field [0001] The invention relates to the field of tumor targeting therapy, and more particularly relates to a polypeptide capable of antagonizing the RNA binding activity of DDX3 protein and its application. Background technique [0002] Tumor is a disease that seriously threatens human life and health. With the process of industrialization, the incidence of tumor is increasing year by year. According to the report of the International Cancer Research Center (IARC): In the next few decades, the number of cancer cases will continue to grow rapidly. It is estimated that there will be 21.36 million new cancer cases and 13.15 million deaths in the world in 2030. The demand for cancer treatment will continue to grow rapidly increase. Traditional surgery, chemotherapy, and radiotherapy are the main means of treating tumors. However, these methods often bring many side effects during treatment, which brings great pain to cancer patients and their families. Therefore, t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/08C07K19/00A61K38/10A61K47/64A61P35/00
CPCA61K38/00C07K7/08C07K2319/10
Inventor 童强松郑丽端杨枫陈亚俊李欢欢叶霖李聃宋华杰
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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