Polypeptide aggregate molecule as well as preparation method and application thereof

A technology of aggregates and molecules, applied in the field of biomedicine, can solve the problems of lack of synthetic raw materials, etc., and achieve the effect of long residence time and inhibition of migration

Active Publication Date: 2021-07-13
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

For example, Hitosugi et al. substituted tyrosine at position 105 of PKM2 with phenylalanine, which prevented PKM2 from being phosphorylated and fixed in a highly active tetramer conformation, resulting in a lack of synthetic raw materials and thus inhibiting tumor growth (see Hitosugi T,Kang S,Heiden M V,et al.TyrosinePhosphorylation Inhibits PKM2 to Promote the Warburg Effect andTumor Growth[J].Science Signaling,2009,2(97):ra73.)

Method used

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  • Polypeptide aggregate molecule as well as preparation method and application thereof
  • Polypeptide aggregate molecule as well as preparation method and application thereof
  • Polypeptide aggregate molecule as well as preparation method and application thereof

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Embodiment 1

[0052] This embodiment provides a polypeptide aggregate molecule, the structure of which is shown in Formula I.

[0053] The preparation method of the polypeptide aggregate molecule comprises the following steps:

[0054] (1) Synthesis of peptides

[0055] Synthesizing a polypeptide containing an enzyme-specific hydrolysis part and an assembly driving part, the molecular formula of the polypeptide is S(GlcNAc)-KLVFF, wherein GlcNAc is acetylglucosamine, S is serine, K is lysine, L is leucine, V is valine, F is phenylalanine;

[0056] Experimental instruments and materials: dimethylformamide (DMF), piperidine, resin, dichloromethane (DCM), ninhydrin reaction reagent (ninhydrin, vitamin C, phenol), tetramethyluronium hexafluorophosphate (HBTU), hexahydropyridine, triisopropylsilane TIS, anhydrous diethyl ether, trifluoroacetic acid (TFA), N-methylmorpholine (NMM), methanol, various amino acids mentioned above, acetylglucosamine serine, azide Acetic acid and peptide solid-phas...

Embodiment 2

[0064] This embodiment provides a polypeptide aggregate molecule, the structure of which is shown in Formula II.

[0065] The preparation method of the polypeptide aggregate molecule comprises the following steps:

[0066] (1) Synthesis of peptides

[0067] This step is with embodiment 1 step (1);

[0068] (2) Click reaction to connect triphenylamine AIE molecules

[0069] Experimental instruments and materials: sodium ascorbate, copper sulfate pentahydrate, DMSO, AIE molecules, flasks, etc.;

[0070] Specific operation method: take the polypeptide synthesized in step (1), sodium ascorbate (0.4eq), copper sulfate pentahydrate (0.4eq), and triphenylamine AIE molecule (2eq) shown in formula II are dissolved in 5mL DMSO, and pass into Under nitrogen protection, react overnight, after the reaction is completed, dialyze and freeze-dry to obtain the aggregate molecule.

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Abstract

The invention relates to a polypeptide aggregate molecule as well as a preparation method and an application thereof. The polypeptide aggregate molecule comprises serine, an enzyme specific hydrolysis part, an assembly driving part and an aggregation-induced emission part, and the serine, the enzyme specific hydrolysis part, the assembly driving part and the aggregation-induced emission part are connected to form the polypeptide aggregate molecule. The polypeptide aggregate molecule can be specifically hydrolyzed in tumor cells, the action of serine and dimer PKM2 is exposed, the polypeptide aggregate molecule is promoted to be converted into tetramer PKM2, and therefore tumor inhibition is achieved, in addition, the aggregation-induced luminescence effect is achieved through assembling, the progress and migration of tumors can be monitored in real time, and meanwhile the long-acting retention effect is achieved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to a polypeptide aggregate molecule and its preparation method and application. Background technique [0002] Prostate cancer is a malignant tumor that occurs in the prostate tissue of men and is the result of abnormal growth of prostatic alveolar cells. There are many treatment methods for prostate cancer. According to different treatment methods, the current treatment methods include chemotherapy, surgery, cryotherapy, radiotherapy, radioactive seed implantation treatment, etc. For cancers that tend to spread throughout the body and advanced cancers that have metastasized, Chemotherapy is the main treatment method at present, however, the resistance of cancer cells to chemotherapeutic drugs often leads to the failure of chemotherapy. [0003] For traditional organic materials, the fluorescence intensity will decrease as the concentration increases. In recent years, a series of a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N9/12A61K38/45A61P35/00
CPCC12N9/1205C12Y207/0104A61K38/45A61P35/00C07K2319/00C07K2319/50
Inventor 李莉莉侯大勇刘秀梅肖五一王浩徐万海
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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