A polypeptide that antagonizes the binding protein of hepatitis B virus X protein, a drug comprising the polypeptide and its application

A hepatitis B virus, protein-binding technology, applied in drug combinations, anti-tumor drugs, peptide/protein components, etc.

Inactive Publication Date: 2021-09-14
HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

No specific inhibitors of HBXIP have been found for the treatment of breast cancer

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 polypeptide that antagonizes the binding protein of hepatitis B virus X protein, a drug comprising the polypeptide and its application
  • A polypeptide that antagonizes the binding protein of hepatitis B virus X protein, a drug comprising the polypeptide and its application
  • A polypeptide that antagonizes the binding protein of hepatitis B virus X protein, a drug comprising the polypeptide and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1 Design of activatable tumor targeting cell penetrating peptide (activatablecellpenetratingpeptide, ACPP)

[0060] Cell penetrating peptides (CPPs) are currently the strongest and fastest transmembrane transport molecules. They have the characteristics of water solubility, low lysis, and enter various cell membranes through non-phagocytosis. They bring new technologies to the treatment of tumors. opportunity. Hairpin-shaped composite CPPs modified on the basis of CPPs are called tumor-targeting CPPs, also known as activatable cellpenetrating peptides (ACPPs).

[0061] The sequence of the ACPP adopted in the present invention is:

[0062] SEQ ID No.7: Val-Ser-Arg-Arg-Arg-Arg-Arg-Arg-Ser-Ser-Arg-Arg-Arg-Arg-Pro-Leu-Gly-Leu-Ala-Gly-Asp-Asp-Asp- Asp-Gly-Gly-Glu-Glu-Glu-Glu-Glu-Glu.

[0063] Structural features: (1) active center CPP region (ValSerArgArgArgArgArgArgArgSerSerArgArgArgArgArg) with cell membrane penetration function (positively charged sequence); (2...

Embodiment 2

[0065] Example 2 Solid phase synthesis and purification of breast cancer treatment polypeptide drug ACPP-RI-HBXIP

[0066] ACPP-RI-HBXIP polypeptide sequence (SEQIDNo.8): Val-Ser-Arg-Arg-Arg-Arg-Arg-Arg-Ser-Ser-Arg-Arg-Arg-Arg-Pro-Leu-Gly-Leu-Ala -Gly-Asp-Asp-Asp-Asp-Gly-Gly-Glu-Glu-Glu-Glu-Glu-Glu-Gly-Pro-Lys-Leu-Ser-Arg-Gln-Glu-Ser-Ala-Glu-Thr -His-Lys-Gly-Asn-Arg-Met-Tyr.

[0067] (1) Materials and reagents

[0068] Fmoc-Tyr(tBu)-Wang resin, substitution value 0.44mmol / g.

[0069] Required protected amino acids: Fmoc-Val-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Met-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Gly- OH, Fmoc-Lys(Boc)-OH, Fmoc-His(Trt)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Glu(OtBu)-OH, Fmoc-Ala-OH, Fmoc-Ser(tBu) -OH, Fmoc-Gln(Trt)-OH, Fmoc-Leu-OH, Fmoc-Pro-OH, Fmoc-Asp(OtBu)-OH, Fmoc-Val-OH.

[0070] Reagents: HOBt, DIC, DMF, piperidine.

[0071] (2) Instruments

[0072] PSI300 peptide synthesizer, Waters high performance liquid chromatography, magnetic stirrer.

[0073] (3) ...

Embodiment 3

[0088]Using surface plasmon resonance technology, the biosensor Biacore T200 biomacromolecular interaction analyzer (manufactured by GE Healthcare) was used to determine the binding force between the synthetic polypeptide ACPP-RI-HBXIP and the recombinantly expressed Recombinant HumanHBXIP protein (Abcam, No. ab130038) in vitro. Determination. Dilute the Recombinant Human HBXIP protein with NaAc with an optimal pH of 5.0, select the optimal dilution and select a channel on the CM5 chip for coupling, the target value of the coupled Recombinant Human HBXIP is 1000RU, and select another channel as a control. The test conditions were 25°C, the flow rate was 20 μL / min, and the buffer was HBS-EP (pH7.4, Bia-Certified). After the chip-coupled RecombinantHuman HBXIP protein reaches the target value, the surface of the chip is blocked, and then the ACPP-RI-HBXIP polypeptide protein is diluted with HBS-EP buffer, and protein samples with different concentrations (6 different concentrati...

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

No PUM Login to view more

Abstract

The invention relates to a polypeptide for antagonizing hepatitis B virus X protein binding protein (HBXIP), comprising the amino acid sequence of SEQ ID No. 1 or an amino acid sequence with 70%-100% similarity to SEQ ID No. 1. The present invention also relates to a pharmaceutical composition comprising the above polypeptide and its application in treating and preventing breast cancer. The functionally active polypeptide of the present invention has the function of inhibiting the activity of HBXIP at the molecular level, cell level and animal level, so it can inhibit the growth and metastasis of breast cancer, and can be widely used in the prevention and treatment of breast cancer.

Description

technical field [0001] The invention relates to a polypeptide antagonizing the binding protein of hepatitis B virus X protein, a medicine containing the polypeptide and application thereof. Background technique [0002] Breast cancer is one of the main malignant tumors that endanger women's health, accounting for about 7%-10% of systemic malignant tumors, seriously threatening women's lives, and is the leading cause of death for women aged 40-60. Among all cancer-related deaths, breast cancer is second only to lung cancer. Since the 20th century, the incidence of breast cancer at home and abroad has been rising to varying degrees, especially in recent years. There are approximately 1.5 million newly diagnosed cases of breast cancer and approximately 560,000 deaths worldwide each year. [0003] With the rapid development of my country's economy, great changes in people's lifestyles, and the aging population and other factors, the annual incidence of breast cancer is increas...

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): C07K7/08C12N15/11A61K38/10A61P35/00
CPCA61K38/00A61P35/00C07K7/08
Inventor 周晓雷朱重悦褚洁张世光邹卫
Owner HEBEI UNIVERSITY OF SCIENCE AND TECHNOLOGY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products