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Polypeptide for specifically targeting human epidermal growth factor receptor 2 (HER2) protein

A kind of specific and targeted technology, applied in the field of preparation of HER2-targeted anti-tumor drugs or imaging preparations, can solve the problems of large toxic and side effects, and achieve the effects of small molecular weight, strong selectivity and high purity

Active Publication Date: 2014-11-05
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, while chemotherapy drugs kill tumor cells, they also kill normal cells in the human body, and the side effects are severe.

Method used

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  • Polypeptide for specifically targeting human epidermal growth factor receptor 2 (HER2) protein
  • Polypeptide for specifically targeting human epidermal growth factor receptor 2 (HER2) protein
  • Polypeptide for specifically targeting human epidermal growth factor receptor 2 (HER2) protein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Synthesis of the polypeptide of the present invention

[0056] 1) Experimental equipment and materials

[0057] Dimethylformamide (DMF), piperidine, resin, dichloromethane (DCM), ninhydrin reagent (ninhydrin, vitamin C, phenol), tetramethylurea hexafluorophosphate (HBTU), six Hydropyridine (piperidine), triisopropylsilane TIS, ethanedithiol (EDT), anhydrous ether, trifluoroacetic acid (TFA), N-methylmorpholine (NMM), methanol, various amino acids, peptides Solid phase synthesis tube.

[0058] 2) Solution preparation

[0059] Deprotection solvent-hexahydropyridine: DMF=1:4

[0060] Reaction liquid——NMM:DMF=1:24

[0061] Lysis Solution——TFA (92.5%), TIS (2.5%), EDT (2.5%), H 2 O(2.5%)

[0062] Ninhydrin test solution——Ninhydrin: Vitamin C: Phenol=1:1:1

[0063] 3) Experimental steps

[0064] Weigh the resin and put it into the peptide solid phase synthesis tube (hereinafter referred to as the reactor), and add an appropriate amount of DMF to swell for more than half an hour...

experiment example 1

[0070] Experimental example 1 Flow cytometry method to detect the binding effect of SEQ ID NO.1 and SEQ ID NO.2 on human HER2-positive breast cancer cells respectively

[0071] 1. Experimental method

[0072] The human breast cancer HER2 high-expressing cell line SKBR3 was collected and suspended in RPMI1640 medium containing 10% heat-inactivated fetal bovine serum. The cell density was 1x10. 6 / mL, aliquot into four 1.5mL EP tubes, 200μL / tube. Add fluorescein isothiocyanate (FITC) labeled SEQ ID NO. 1, SEQ ID NO. 2, anti-HER2 antibody (ebioscience, BMS120FI), the final concentration is 50μmoL / L, the control group uses the same amount of 0.01 as the polypeptide mM PBS (phosphate buffer pH 7.4) instead of polypeptide. After 30 minutes of incubation in a dark ice bath, the cells were collected by centrifugation at 1000g for 4 minutes, washed with 1mL PBS, washed twice, 500μL PBS was added, mixed, and the fluorescence intensity and binding ratio were measured by flow cytometry.

[007...

experiment example 2

[0075] Experimental example 2 Flow cytometry method to detect the binding effect of SEQ ID NO.1 and SEQ ID NO.2 on human HER2-negative breast cancer cells respectively

[0076] 1. Experimental method

[0077] The human breast cancer HER2 low-expressing cell line MCF-7 was collected and suspended in H-DMEM culture medium containing 10% heat-inactivated fetal bovine serum at a cell density of 1x10 6 / mL, divided into four 1.5 mL EP tubes. 200μL / tube. Add fluorescein isothiocyanate (FITC) labeled SEQ ID NO.1, SEQ ID NO.2, and anti-HER2 antibody (ebioscience, BMS120FI), the final concentration is 50μmol / L, the control group uses the same amount of 0.01 as the polypeptide mM PBS (phosphate buffer pH 7.4) instead of polypeptide. After 30 minutes of incubation in a dark ice bath, the cells were collected by centrifugation at 1000 g for 4 minutes, washed with 1 mL of PBS, and washed twice, then 500 μL of PBS was added, mixed, and the fluorescence intensity and binding ratio were measured...

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Abstract

The invention relates to a polypeptide for specifically targeting a human epidermal growth factor receptor 2 (HER2) protein. The polypeptide is shown in the following general formula 1 of X1X2X3X4X5X6X7RX8YWX9X10X11X12X13X14X15X16X17RX18X19X20X21YX22. The invention also relates to a nucleotide sequence for coding the polypeptide, an expression vector for expressing the polypeptide and a host cell. The invention also relates to the polypeptide and its bivalent or multivalent, a pharmaceutical composition prepared from the polypeptide or its bivalent or multivalent as a targeting polypeptide, a preparation for killing cancer cells and a developing agent, and a use of the polypeptide and its bivalent or multivalent. The polypeptide has HER2 positive cell targeting effects and strong selectivity. The polypeptide can be prepared by a chemical synthesis method and has the advantages of high purity, small molecular weight, strong singularity, no immunogenicity, safety and reliability.

Description

Technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to a polypeptide, in particular to a polypeptide that specifically targets the HER2 protein and a product derived from the peptide that can bind to the HER2 protein, and the above-mentioned polypeptides or products derived therefrom are used in the preparation of targets Application to HER2 anti-tumor drugs or imaging preparations. Background technique [0002] Cancer is a major cause of death in the world. Data show that there were approximately 14.1 million new cancer cases worldwide in 2012, and the number of cancer deaths reached 8.2 million, compared with 12.7 million and 7.6 million in 2008. The most common cancers diagnosed worldwide are lung cancer (1.8 million, 13%), breast cancer (1.7 million, 11.9%) and colorectal cancer (1.4 million, 9.7%). The most common cause of death is lung cancer (1.6 million, 19.4%), liver cancer (800,000, 9.1%) and gastric cancer (700,000, ...

Claims

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Application Information

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IPC IPC(8): C07K14/00C12N15/11A61K47/42A61K47/48A61K51/08A61K49/00A61P35/00
CPCA61K47/42A61K47/62A61K49/00A61K51/08C07K14/00
Inventor 耿令令方巧君胡志远连文玺杨小亮
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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