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Targeted PD-L1IgV affinity peptide D2 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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  • Targeted PD-L1IgV affinity peptide D2 with anti-tumor activity
  • Targeted PD-L1IgV affinity peptide D2 with anti-tumor activity
  • Targeted PD-L1IgV affinity peptide D2 with anti-tumor activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] The D-configuration affinity peptide D2 of PD-L1 IgV with anti-tumor activity provided by the present invention, which specifically binds to the PD-L1 IgV region, is screened by mirror-image phage display peptide library technology, and its amino acid sequence is:

[0025] Lys-His-Ala-His-His-Thr-His-Asn-Leu-Arg-Leu-Pro, namely K-H-A-H-H-T-H-N-L-R-L-P, with a molecular weight of 1459.8.

[0026] 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 imp...

Embodiment 2

[0059] The D-configuration affinity peptide D2 of the PD-L1 IgV with anti-tumor activity is synthesized by the Fomc solid-phase peptide synthesis method, and the synthesis steps are briefly described as follows:

[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 ...

Embodiment 3

[0109] Taking the D-configuration affinity peptide D2 of 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 D2 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 D2 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 mice were ...

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Abstract

The invention belongs to the technical field of biological pharmacy, and in particular relates to a targeted PD-L1IgV D-configured affinity peptide D2 product with anti-tumor activity, and a preparation method and application of the targeted PD-L1IgV D-configured affinity peptide D2 product. The affinity peptide D2 is specifically bonded in a PD-L1IgV region; the amino acid sequence of the affinity peptide D2 is KHAHHTHNLRLP; the molecular weight of the affinity peptide D2 is 1459.8; the affinity peptide D2 is prepared by virtue of a Fomc solid-phase polypeptide synthesis method; the affinity peptide D2 serving as the main active component plays a role in preparation of anti-colon-cancer drugs. The affinity peptide D2 provided by the invention is obtained by displaying the peptide library screening technology by utilizing mirrored phage and carrying out high-throughput screening by taking D-PD-L1IgV as the target spot. The tumor-burdened experiments in mice prove that the affinity peptide D2 has better anti-tumor activity and is capable of obviously inhibiting the growth of tumor in mice, and therefore, a novel idea and a theoretical basis are provided for researching and developing PH-L1-based drugs.

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 targeting PD-L1 IgV with anti-tumor activity Affinity peptide D2 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 me...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08A61K38/10A61P35/00C07K1/06C07K1/04
Inventor 高艳锋刘蓓媛祁元明李国栋
Owner ZHENGZHOU UNIV
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