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Anti-tumor polypeptide sur-x targeting survivin-xiap complex and its use

A technology of sur-x and compound, applied in the field of -XIAP compound, can solve the problems of increased expression of XIAP and increased risk of tumor recurrence

Active Publication Date: 2021-04-20
THE FIRST HOSPITAL OF CHINA MEDICIAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In patients with basal-like breast cancer, XIAP expression is elevated and the risk of tumor recurrence is significantly increased

Method used

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  • Anti-tumor polypeptide sur-x targeting survivin-xiap complex and its use
  • Anti-tumor polypeptide sur-x targeting survivin-xiap complex and its use
  • Anti-tumor polypeptide sur-x targeting survivin-xiap complex and its use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033]Example 1 Synthesis, Purification and Molecular Measurement of Polypeptide S

[0034]The anti-tumor polypeptide S in the present invention is a particular amino acid sequence that binds to XIAP according to the uneven document, and is incorporated herein by reference. The final sequence is in SEQ ID NO: 1. Select a peptide segment that does not expressly expresses in human cells as a control of the polypeptide S having a specific anti-tumor of the present invention, which is recorded as a polypeptide CON, and its final sequence is seen in SEQ ID NO: 2. The polypeptide NS is a shortened polypeptide S to obtain a residue of two-thirds of the S amino group. The final sequence of the NS is shown in SEQ ID NO: 3. Both polypeptides S, CON and NS were synthesized by FMOC solid peptide synthesis, as follows: According to the polypeptide sequence, the peptide chain is delayed from the carboxy terminal to the amino terminal, and after the peptide is synthesized, the 95 cutting fluid (three...

Embodiment 2

[0037]Example 2 Observation of the polypeptide under the copolymerization microscope can enter the cell

[0038]HoecHst33342 was treated with a polypeptide into a cell under a copolymerized microscope at a common focusing microscope at a copolymerized microscope to treat human colorectal cancer cells HCT 116 and RKO 1H at a ratio of 1: 1000.

[0039]image 3 The polypeptide S and CON can be observed to be observed under a copolymerized microscope, and the polypeptide S has a good film passivity.

Embodiment 3

[0040]Example 3MTT Detection S on the human nuts rectal cancer cell line HCT116 and RKO, human gastric cancer cell line MGC-803 and MKN45, and human normal cell line SV5 cell viability

[0041]The logarithmic cells, counting cells were collected, and the cell concentration was adjusted, and in 5,000 cells / well were seeded in a 96-well culture plate; set the experimental group (S) and a negative control group (CON), each set of concentration gradients: 0, 2.5 μm, 5 μm, 10 μm, 15 μm, 20 μm, each concentration of 3 complexificial holes; after the cell is attached, the corresponding treatment is given, for 6 h, 24 h, respectively; 20 μl of MTT (5 g / L), incubation at 37 ° C After 4 hours, the supernatant was given, and 200 μl of dimethyl sulfoxide (DMSO) was added, and the absorbance (OD) value of the 570 nm wavelength was measured; the cells were relatively viable under different concentrations; repeated three times.

[0042]Figure 4 It is shown as the effect of HCT116 and RKO, human gast...

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PUM

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Abstract

The present invention relates to the field of targeted therapeutic drugs for tumors, in particular to an anti-tumor polypeptide Sur-X based on targeting survivin-XIAP complex, and its application in the treatment of various tumors including colorectal cancer and gastric cancer . The anti-tumor polypeptide Sur-X of the present invention can rapidly and efficiently induce the death of colorectal cancer and gastric cancer cells by inhibiting the formation of the survivin-XIAP complex, and has no effect on normal human cells, thereby exerting the therapeutic effect of specifically targeting tumor cells. In addition, the polypeptide is easy to synthesize in vitro, which is convenient for clinical application. Therefore, the polypeptide Sur‑X has potential commercial value and can be widely used in the field of tumor targeting therapy technology.

Description

Technical field[0001]The present invention relates to a tumor targeting therapeutic pharmaceutical sector, and more particularly to a polypeptide drug SUR-X designed based on a survivin-xiap complex, and their applications in a variety of tumors including colorectal cancer and gastric cancer. It is particularly related to SUR-X by interfering with the formation of Survivin-XIAP complexs, promoting apoptosis and procedural necrosis of tumor cells, and exerts the role of tumor targeting treatment.Background technique[0002]In recent decades, with the extension of human average life, the change in living environment and lifestyle, cancer has become the first killer that threatens human life. Global Cancer Statistics (Globocan) showed that there were 18.1 million cancer new cases and 9.6 million cancer deaths in 2018. Among them, the incidence of colorectal cancer and gastric cancer ranked third and fifth, and the sum of two is 15.9%. In addition, the mortality rate of colorectal cancer ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/16A61K47/64A61P35/00
CPCA61K38/00A61P35/00C07K14/4747C07K14/82C07K2319/10
Inventor 车晓芳刘云鹏曲秀娟方婉侠
Owner THE FIRST HOSPITAL OF CHINA MEDICIAL UNIV