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PD-L1IgV-targeting affinity peptide D1 with anti-tumor activity

An anti-tumor activity and targeted technology, applied in anti-tumor drugs, medical preparations containing active ingredients, peptides, etc.

Active Publication Date: 2014-07-23
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the use of PD-L1 blockers as tumor immunotherapy drugs or adjuvants has good application prospects and safety, but in the prior art, there is still a lack of better PD-L1 blocker products

Method used

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  • PD-L1IgV-targeting affinity peptide D1 with anti-tumor activity
  • PD-L1IgV-targeting affinity peptide D1 with anti-tumor activity
  • PD-L1IgV-targeting affinity peptide D1 with anti-tumor activity

Examples

Experimental program
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Effect test

Embodiment 1

[0024] The D-configuration affinity peptide D1 targeting PD-L1 IgV with anti-tumor activity provided by the present invention specifically binds to the PD-L1 IgV region and is screened by mirror-image phage display peptide library technology. Its amino acid sequence It is: Asn-Tyr-Ser-Lys-Pro-Thr-Asp-Arg-Gln-Tyr-His-Phe, namely N-Y-S-K-P-T-D-R-Q-Y-H-F, with a molecular weight of 1554.7.

[0025] Since the peptides obtained by conventional phage display peptide library screening are composed of natural amino acid residues, they are easily degraded by enzymes and have a short half-life in vivo. Therefore, we selected the PD-L1 IgV region protein artificially synthesized from D-configuration amino acids as the target, and screened D-configuration antagonistic peptides through mirror phage display technology, thereby greatly improving its ability to resist enzymatic degradation. Prolong the half-life of action in vivo. For the convenience of those skilled in the art to implement ...

Embodiment 2

[0059] The D-configuration affinity peptide D1 of the PD-L1 IgV with anti-tumor activity is synthesized by Fomc solid-phase peptide synthesis method.

[0060] The main reagents used in the synthesis process are:

[0061] Heading liquid: acetic anhydride / pyridine solution (1:1 v / v);

[0062] Indene detection reagent: A. Ninhydrin / ethanol solution (5% w / v), B. Phenol / ethanol (4:1 w / v), C. Potassium cyanide / pyridine (2% v / v);

[0063] Deprotection solution: piperidine / DMF solution (20% v / v);

[0064] Cleavage reagent: by volume, TFA (82.5%), H 2 O (5%), phenol (5%), thioanisole (5%), ethanedithiol (2.5%).

[0065] The synthetic steps are briefly described as follows:

[0066] (1) Swell the resin, add the first amino acid

[0067] A. Swelling resin: Take 0.3~0.5 g Rink resin (the C-terminal amino acid of the peptide connected to the resin is an amide) and place it in a cleaned and dried peptide synthesizer, add an appropriate amount of DMF, soak for about 30 minutes to ful...

Embodiment 3

[0109] Taking the D-configuration affinity peptide D1 targeting PD-L1 IgV with anti-tumor activity prepared in Example 2 as an example, the inventors conducted further in vivo experiments on tumor-bearing mice. The specific experimental process is as follows:

[0110] (1) Affinity peptide D1 inhibits the growth of transplanted tumors in mice bearing CT26 colon cancer

[0111] Select 24 experimental Balb / c mice, adjust the cell concentration to 5×10 mouse colon cancer (CT26) cells with normal saline (NS) 6 cells / mL, 0.1 mL cell suspension (containing 5×10 5 cells) were inoculated subcutaneously in the armpit of the right forelimb of each Balb / c mouse, and the growth of the subcutaneous tumor was continuously observed.

[0112] The affinity peptide D1 prepared in Example 2 was dissolved in physiological saline to make a polypeptide drug, which was subpackaged and stored at -20°C for future use. Nine days after inoculation with mouse-derived colon cancer (CT26) cells, the mic...

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Abstract

The invention belongs to the technical field of bio-pharmacy and specifically relates to a PD-L1IgV-targeting D-configuration affinity peptide D1 product with anti-tumor activity, as well as preparation and application thereof. The affinity peptide D1 is specifically bound to a PD-L1IgV region, the amino acid sequence is NYSKPTDRQYHF, and the molecular weight is 1554.7. The affinity peptide D1 is prepared through a Fomc solid-phase polypeptide synthesis method, and plays a role in preparation of anti-colon cancer medicaments as a main active ingredient. The affinity peptide D1 provided by the invention is obtained by utilizing a mirroring bacteriophage display peptide library screening technology and performing high-throughput screening by taking PD-L1IgV as a target point. Through tumor-bearing experiments in mouse bodies, the inventor proves that the affinity peptide D1 has better anti-tumor activity and can obviously inhibit the growth of tumors in the mouse bodies, so that a new idea and theoretical basis are provided for researching and developing PD-L1-based medicaments.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and specifically relates to the screening, preparation and application of a polypeptide product with anti-tumor activity. More specifically, the invention relates to a D-configuration protein targeting PD-L1IgV with anti-tumor activity. And peptide D1 product and its preparation and application. Background technique [0002] In recent years, the situation of tumor prevention and control is very severe. With the improvement of clinical diagnosis, surgical treatment, chemotherapy and radiotherapy, some patients can get early detection, early treatment, and better prognosis. However, finding new treatment methods and drugs has always been a global challenge. Research hotspots. Compared with traditional treatment methods, tumor immunotherapy can activate or induce tumor patients to establish a specific immune response to tumor antigens, eliminate primary tumor cells, and establish immune...

Claims

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Application Information

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IPC IPC(8): C07K7/08C07K1/04A61K38/10A61P35/00
Inventor 高艳锋刘蓓媛祁元明李国栋
Owner ZHENGZHOU UNIV
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