Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

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
View PDF2 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 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

Examples

Experimental program
Comparison scheme
Effect test

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...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
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
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com