Preparation method of polypeptide supramolecular Bcl-xL antagonist nano-drug with mitochondrial targeting property

A nano-drug, bcl-xl technology, applied in the preparation method of peptides, nano-drugs, organic active ingredients, etc., can solve problems such as inducing cancer, and achieve the effects of enhancing membrane permeability, mild reaction conditions, and simple preparation method

Active Publication Date: 2021-05-28
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But on the other hand, anti-apoptotic proteins may block the induction and execution of apoptosis through the process of heterodimer association in the aforementioned mechanism, thereby inducing cancer

Method used

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  • Preparation method of polypeptide supramolecular Bcl-xL antagonist nano-drug with mitochondrial targeting property
  • Preparation method of polypeptide supramolecular Bcl-xL antagonist nano-drug with mitochondrial targeting property
  • Preparation method of polypeptide supramolecular Bcl-xL antagonist nano-drug with mitochondrial targeting property

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Experimental program
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Embodiment 1

[0045] This embodiment provides a preparation method of a polypeptide supramolecular Bcl-xL antagonist nanomedicine with mitochondrial targeting, the preparation process comprising:

[0046] S1: Synthesis by solid-phase synthesis: phenylalanine-phenylalanine-4-aminoproline-phenylalanine-picoline alanine, glycine-glutamine-valine-glycine -Arginine-Glutamine-Leucine-Alanine-Isoleucine-Isoleucine-Glycine-Aspartic Acid-Aspartic Acid-Isoleucine-Asparagine-Arginine Acid-phenylalanine-phenylalanine-4-aminoproline-phenylalanine-picoline alanine, camptothecin-phenylalanine-phenylalanine-4-aminoproline For the three polypeptide sequences of acid-phenylalanine-picoline alanine, the feeding amount is 0.25 mmol, and the yield is 90%. It is separated and purified by high-performance liquid chromatography, and the product purity is more than 99%.

[0047] S2: Phenylalanine-phenylalanine-4-aminoproline-phenylalanine-picoline alanine, glycine-glutamine-valine-glycine-arginine-glutamine Amide...

Embodiment 2

[0049] This embodiment provides a preparation method of a polypeptide supramolecular Bcl-xL antagonist nanomedicine with mitochondrial targeting, the preparation process comprising:

[0050] S1: Synthesis by solid-phase synthesis: phenylalanine-phenylalanine-4-aminoproline-phenylalanine-picoline alanine, glycine-glutamine-valine-glycine -Arginine-Glutamine-Leucine-Alanine-Isoleucine-Isoleucine-Glycine-Aspartic Acid-Aspartic Acid-Isoleucine-Asparagine-Arginine Acid-phenylalanine-phenylalanine-4-aminoproline-phenylalanine-picoline alanine, camptothecin-phenylalanine-phenylalanine-4-aminoproline For the three polypeptide sequences of acid-phenylalanine-picoline alanine, the feeding amount is 0.25 mmol, and the yield is 90%. It is separated and purified by high-performance liquid chromatography, and the product purity is more than 99%.

[0051] S2: Phenylalanine-phenylalanine-4-aminoproline-phenylalanine-picoline alanine, glycine-glutamine-valine-glycine-arginine-glutamine Amide...

Embodiment 3

[0053] The mitochondrial-targeting polypeptide supramolecular Bcl-xL antagonist nanomedicine prepared in Example 2 of the present invention was used to detect the cell uptake by flow cytometry.

[0054] Taking HeLa cells as an example, in a confocal glass dish in DMEM medium at 1.2×10 5 HeLa cells were cultured at a density of 24 hr. The cells were washed three times with PBS, and fresh serum-free medium containing FAM-labeled polypeptide supramolecular nanomedicine was added, and the culture was continued for 2, 4, 8 or 10 hours. After washing the cells twice with PBS, the cells were fixed with 4% paraformaldehyde for 20 min and stained with DAPI for 20 min. Observation by confocal laser scanning microscope, as Figure 4 shown. We also assessed the cellular uptake of peptide supramolecular nanomedicines by flow cytometry. HeLa cells seeded on a 6-well plate (1.5 × 10 per well 5 cells) in CO 2 Incubate at 37°C for 24 hours under atmosphere. The cells were washed with PB...

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Abstract

The invention discloses a preparation method of a polypeptide supramolecular Bcl-xL antagonist nano-drug with mitochondrial targeting, and relates to the technical field of supramolecular nano-drugs. Based on peptide sequences with mitochondrial targeting and pH-responsive morphologic changes in the tumor microenvironment, a BH3 structural domain derived from pro-apoptotic protein and anti-cancer, anti-inflammatory and antibacterial drugs are connected to polypeptide through covalent bonds, and the supramolecular Bcl-xL antagonist nano-drug is obtained by co-assembling the BH3 structural domain, the anti-cancer, anti-inflammatory and antibacterial drugs and the polypeptide according to different component proportions. The polypeptide supramolecular Bcl-xL antagonist nano-drug disclosed by the invention has the advantages that the polypeptide supramolecular Bcl-xL antagonist nano-drug has excellent mitochondrial targeting property and tumor microenvironment pH responsive morphology transformation, and has good tumor targeting enrichment capacity and excellent anti-tumor treatment effect. The preparation method is simple, easy for industrial production and wide in application field range.

Description

technical field [0001] The invention relates to the technical field of supramolecular nanomedicine, in particular to a preparation method and application of a polypeptide supramolecular Bcl-xL antagonist nanomedicine with mitochondrial targeting. [0002] technical background [0003] Cancer remains one of the most pressing public health problems. In order to achieve effective specific therapy and minimize adverse side effects, subcellular organelle-targeted cancer therapeutic strategies with more precise and active targeting functions have attracted great research interest and have broad implications in the fields of cancer therapy and precision medicine. Prospects. Mitochondria are one of the key organelles that maintain many fundamental physiological processes. The critical role of mitochondria in regulating cell survival would contribute to the carcinogenesis of different cancers when apoptosis induced by mitochondrial dysfunction is inhibited. Mitochondria thus consti...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K31/337A61K31/4745A61K31/704A61P15/00A61P29/00A61P35/00B82Y5/00C07K1/00C07K1/04C07K1/06
CPCA61K47/64A61K31/4745A61K31/337A61K31/704A61P35/00A61P15/00A61P29/00C07K1/04C07K1/06C07K1/00B82Y5/00Y02P20/55
Inventor 余志林李明明
Owner NANKAI UNIV
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