Polypeptide molecule for preventing PD-L1 from redistributing on tumor surface, and preparation and application of polypeptide molecule

A molecular and polypeptide sequence technology, applied in the field of medicine, can solve problems such as redistribution, poor tumor permeability, and large molecular weight, and achieve the effects of avoiding redistribution, reducing antibody systemic toxicity, and improving blocking effect

Inactive Publication Date: 2020-06-30
BEIJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above immune checkpoint inhibitors have problems such as redistribution of PD-L1 on the tumor cell membrane, large molecular weight, and poor tumor permeability, making it difficult to achieve effective tumor treatment

Method used

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  • Polypeptide molecule for preventing PD-L1 from redistributing on tumor surface, and preparation and application of polypeptide molecule
  • Polypeptide molecule for preventing PD-L1 from redistributing on tumor surface, and preparation and application of polypeptide molecule
  • Polypeptide molecule for preventing PD-L1 from redistributing on tumor surface, and preparation and application of polypeptide molecule

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Embodiment 1: the design of target molecule

[0045] In the following examples, the polypeptide sequence is synthesized by the polypeptide solid-phase synthesis method, and the experimental materials required for the synthesis include: dimethylformamide (DMF), piperidine, Wang resin, dichloromethane (DCM), ninhydrin reaction Reagents (ninhydrin, vitamin C and phenol), benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), hexahydropyridine, triisopropylsilane ( TIS), ethanedithiol (EDT), anhydrous ether, trifluoroacetic acid (TFA), N-methylmorpholine (NMM), N-fluorenylmethoxycarbonyl-6-aminocaproic acid (Fmoc-e-Acp -OH), methanol, amino acid, peptide solid phase synthesis tube, etc.

[0046] In the following examples, the following solutions need to be prepared when using the polypeptide solid-phase synthesis method: deprotection solution - mix hexahydropyridine and DMF at a volume ratio of 1:4; reaction solution - mix NMM and DMF at a volume ratio of 1...

Embodiment 2

[0054] Example 2: Verification of Aggregation

[0055] In this example, the aggregation property is verified by using the polypeptide molecules provided in Example 1.

[0056] The experimental steps are as follows: dissolve the polypeptide molecules in dimethyl sulfoxide (DMSO) to prepare the mother solution, make it fully dispersed, and present a monodisperse state. By mixing the volume of water and DMSO, prepare mixed solutions with different ratios of 0:100, 10:90, 30:70, 50:50, 70:30, and 90:10, and the concentration of the material is 3.0×10 -5 M. A UV spectrophotometer (LAMBDA650, U.S., PerkinElmer, USA) was used to detect the absorbance of the target molecule at different water contents, and the absorbance-wavelength curve was drawn. The result is as figure 1 As shown, there is a peak at 350 and an intersection at 410. With the increase of the water content, the material showed a gradually decreasing trend in the range of 410-300 nm, a rising trend in the range of 4...

Embodiment 3

[0057] Example 3: Verification of Assembly Conditions

[0058] In this example, the polypeptide molecules provided in Example 1 are used to verify the assembly properties.

[0059] The morphology of the polypeptide molecules was observed with a transmission electron microscope (lanthanum hexaboride transmission electron microscope, Tecnai G2 20 S-TWIN (T-20), American FEI Company). The selected concentration is 3.0×10 -5 M target molecule solution, when PD-L1 protein is not added, such as image 3 (a) shows the morphology of nanospheres. After the protein was added, the nanospheres disintegrated and gradually self-assembled to form nanofibers. Such as image 3 (b) shows that at 2 h, through the interaction of intermolecular hydrogen bonds, III interaction occurs to form nanofibers.

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Abstract

The invention discloses a polypeptide molecule for preventing PD-L1 from redistributing on a tumor surface, and a preparation and application of the polypeptide molecule. The polypeptide molecule comprises an aggregation unit part, an assembly unit part and a targeting unit part, wherein the three parts are sequentially connected together to form a long-straight-chain polypeptide compound, and theaggregation unit part and the targeting unit part are respectively positioned at two ends of the long-straight-chain polypeptide compound. The aggregation unit part comprises double-pyrene molecules;the assembly unit part is a polypeptide sequence with an assembly function; and the targeting unit part is a specific polypeptide sequence. The polypeptide molecules dissolves nanospheres through interaction of receptors, polypeptide nanofibers are constructed through in-situ self-assembly in tumor tissues, and long-acting blocking of an immune checkpoint is realized, so that redistribution caused by endocytosis at the immune checkpoints is avoided, and the treatment effect of lasting blocking is achieved.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a polypeptide molecule that prevents immune checkpoints from being redistributed on the surface of tumor cell membranes and its preparation method and application. Background technique [0002] The development of tumors has undergone a series of major changes, from traditional surgical treatment to radiotherapy and chemotherapy, to targeted therapy, and to the recently emerging immunotherapy. At present, immunotherapy has achieved remarkable results in the treatment of various types of tumors, including: breast cancer, bladder cancer, etc. [0003] Cancer immunotherapy (Cancer immunotherapy, CIT) has long-lasting and extensive anti-tumor effects, and aims to inhibit tumor growth and metastasis by regulating the human immune system. Immune checkpoint (Immune checkpoint) is an inhibitory signaling pathway in the immune system, which can regulate the intensity and persi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/08C07K1/04C07K1/06C07K1/107A61K38/10A61P35/00
CPCC07K7/08A61P35/00A61K38/00
Inventor 胡利明肖五一王浩
Owner BEIJING UNIV OF TECH
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