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A kind of polypeptide and its application

A kind of use, amino acid technology, applied in the field of anti-tumor, can solve problems such as technical difficulties, clinical application limitations, recurrence, etc.

Active Publication Date: 2021-05-18
香港城市大学深圳研究院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, liver cancer is a common cancer with a high mortality rate. Drugs commonly used to treat liver cancer include doxorubicin (doxorubicin), cisplatin (cisplatin), and 5-Fluorouracil (fluorouracil) to kill tumor cells through apoptosis, but Up to 72% of patients carry multidrug resistance genes, contributing to treatment failure and relapse
The latest oral drug Sorafenib (Sorafenib) launched in 2005 is a multi-target multi-kinase inhibitor. Compared with placebo treatment, Sorafenib only prolongs the overall survival rate of patients with advanced liver cancer for about 3 months, and the treatment plan is not yet available. ideal
The fly in the ointment is that TAP21 is too long (81 amino acids), which leads to (1) short half-life and requires daily administration; (2) potential immune response; (3) high preparation cost; (4) technical difficulties
Therefore, to some extent, the clinical application of TAP21 is greatly limited
Although this research has been awarded a Chinese patent (patent application number: 201010110980.2, patent name: anti-tumor nucleic acid and polypeptide and their application), there is still a considerable distance from the development of anti-cancer drugs

Method used

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  • A kind of polypeptide and its application
  • A kind of polypeptide and its application
  • A kind of polypeptide and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1 Reference flow for polypeptide synthesis

[0070] 1.1. Raw materials:

[0071] Protected amino acid: Amino acid raw materials are used. If D-type or beta-type polypeptides are synthesized, D-type or beta-type amino acid raw materials are used for the following synthesis procedures.

[0072] Starting resin: Fmoc-Pro-2Cl-Trt-Cl-Resin.

[0073] Condensing agent and organic base: HBTU, NMM.

[0074] Solvents: DMF, DCM, methanol, hexahydropyridine.

[0075] 1.2. Equipment and instruments:

[0076] 80mL glass reaction column, vacuum water pump, dry heater, low-grade large-capacity centrifuge, constant temperature shaker, vacuum drying dish.

[0077] 1.3. Preparation of various reagents:

[0078] (1) Preparation of Kaiser test reagent

[0079] Liquid A: 80% phenol + 20% absolute ethanol

[0080] Solution B: redistilled pyridine

[0081] Solution C: 5g ninhydrin + 100ML absolute ethanol

[0082] (2) Preparation of deprotection solution:

[0083] 20% Hexahydr...

Embodiment 2

[0158] Example 2 Cell experiment

[0159] Chemicals and reagents: Dulbecco's Modified Eagle Medium (DMEM) and Gene TailorSite-Directed Mutagenesis System were purchased from Invitrogen (CA, USA). Fetal bovine serum (FBS) was from HyClone Laboratories, Inc (USA), while restriction enzymes and DNA ligase were purchased from New England BioLabs Inc (USA). Dimethylsulfoxide (DMSO) was purchased from Sigma.

[0160] Cell culture: HepG2, Huh7, Hep3B and rhabdomyosarcoma (RD) cells were maintained in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% fetal bovine serum (FBS) and 1% penicillin and streptomycin, and in 37°C in humidified 5% carbon dioxide.

[0161] First, the biological activity of the polypeptide is tested in vitro. MTT (USE) assay was used to detect cell proliferation. First, HepG2 (ATCC) cells were planted in a 96-well plate, and each well contained 5×10 3 Each well contains 100 μL DEM of 10% FBS, leaving 8 wells blank as a blank control. Incubate (37°C, ...

Embodiment 3

[0165] The biological activity of polypeptide 19 was assessed in vivo. BALB / c nude mice (15g-20g) were used, and 2x106 tumor cells BEL7404 were subcutaneously injected on the back, with 6 mice in each group, and a control group was injected with PBS and a positive control group of peptides. When the tumor volume is 50mm 3 Around 100 days, 100ug or an equal volume of control reagent was injected every day at the tumor site. After 10 days, the injection was stopped and measurements were continued for 10 days. The tumor size was measured at intervals of 3 days, the results were recorded, and the tumor growth curve was drawn with time as the abscissa and volume as the ordinate. from Figure 7 The results showed that, compared with the control group, the tumor volume of the group injected with the active polypeptide was significantly reduced, the tumor volume was small, and the changes had obvious significance. Moreover, the modified polypeptide has a significantly better inhib...

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Abstract

The invention provides a polypeptide and its application. The polypeptide includes a linear polypeptide with a membrane-penetrating peptide (as shown in SEQ ID NO: 1 to SEQ ID NO: 5), a cyclic polypeptide without a membrane-penetrating peptide (as shown in SEQ ID NO: 6 to SEQ ID NO: 8) ) and one or more of mutant polypeptides (shown in SEQ ID NO: 9, SEQ ID NO: 11 to SEQ ID NO: 22). The polypeptide of the present invention shortens the peptide segment of TAP21 in the previous application, and can maintain the original activity and have higher activity, reducing the difficulty of the process and the synthesis cost; it has good anti-tumor properties in cells and animal models , and the effect is obviously better than the existing polypeptide products, and its application in inhibiting tumor or blocking tumor cell proliferation provides a good prospect for anti-tumor therapy.

Description

technical field [0001] The invention belongs to the field of anti-tumor technology, and in particular relates to target-specific anti-tumor polypeptide and application thereof. Background technique [0002] At present, cancer has become an important public health problem worldwide, with nearly 14 million new cases worldwide in 2012, and it is expected that the number of new cases will increase by about 70% in the next 20 years. The cost of treating cancer has also increased over the past decade, but several cancer types still have high mortality rates, for example, liver cancer and uterine cancer. In addition, the morbidity and mortality of cancer and tumors in my country have also been rising, which is also one of the major public health problems in our country. For example, liver cancer is a common cancer with a high mortality rate. Drugs commonly used to treat liver cancer include doxorubicin (doxorubicin), cisplatin (cisplatin), and 5-Fluorouracil (fluorouracil) to kill...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/47A61K38/17A61P35/00A61P35/02
CPCA61K38/00A61P35/00A61P35/02C07K14/4703
Inventor 何明亮陈缨周方行
Owner 香港城市大学深圳研究院