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

A kind of nucleic acid aptamer drug conjugate and its preparation method and use

A nucleic acid aptamer and drug conjugate technology, applied in the field of medicine, can solve the problems of poor tissue penetration, immunogenicity and high preparation cost

Active Publication Date: 2022-07-01
HUNAN UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although antibodies have been developed for decades, only four antibody-drug conjugates have been approved by the FDA at present. A large part of the reason is that the antibody has a large molecular weight, poor tissue penetration, and immunogenicity. High cost of preparation

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
  • A kind of nucleic acid aptamer drug conjugate and its preparation method and use
  • A kind of nucleic acid aptamer drug conjugate and its preparation method and use
  • A kind of nucleic acid aptamer drug conjugate and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0073] The second aspect of the present invention provides the preparation method of the nucleic acid aptamer-drug conjugate provided in the first aspect of the present invention, comprising: connecting a drug molecule with a nucleic acid fragment to provide the nucleic acid aptamer-drug conjugate. The nucleic acid fragment can be a nucleic acid fragment modified with -SH at the 5' end, and the specific method for modifying the nucleic acid fragment with -SH can refer to the literature given above.

[0074] In the preparation method of the nucleic acid aptamer drug conjugate provided by the present invention, the preparation method may specifically include: 1) modifying the linker molecule with a drug molecule containing a aziridine group; 2) modifying the The drug molecule with the linker is reacted with the -SH modified nucleic acid fragment to provide the nucleic acid aptamer drug conjugate.

[0075] In the preparation method of the nucleic acid aptamer drug conjugate provi...

Embodiment 1

[0091] Preparation of mitomycin C benzyl carbonate aptamer:

[0092] a. Preparation of 4-nitrophenyl-4-(2-dimercaptopyridyl)benzyl carbonate:

[0093] To a 50mL three-necked round bottom flask, add LiAlH suspended in 10mL anhydrous tetrahydrofuran 4 74 mg (1.95 mmol), nitrogen protection and 100 mg (0.65 mmol) o-mercaptobenzoic acid dissolved in 10 mL of anhydrous tetrahydrofuran were added in an ice-water bath, then the ice-water bath was removed, and the reaction was stirred at room temperature for 6 h, and the reaction progress was monitored by TLC. When the o-mercaptobenzoic acid was completely converted into o-mercaptobenzyl alcohol, slowly add ice water to quench the reaction, add 2mM hydrochloric acid solution to adjust the pH of the solution to 2, and then extract three times with ethyl acetate / saturated brine = 1:1 system, collect the The organic phase was dried over anhydrous sodium sulfate, and then ethyl acetate was removed by rotary evaporation under reduced pre...

Embodiment 2

[0104] Preparation of mitomycin C ethyl carbonate aptamer:

[0105] a. Preparation of 4-nitrophenyl-4-(2-dimercaptopyridyl)ethyl carbonate:

[0106] 88 mg (0.4 mmol) of 2,2'-dimercaptopyridine and 31.3 mg (0.4 mmol) of 2-mercaptoethanol were added to a 50 mL three-necked round bottom flask, and 10 mL of dichloromethane was added. It was stirred at room temperature for 2 h, and the reaction process was monitored by TLC. The dichloromethane was removed by rotary evaporation under reduced pressure, and the reaction was purified by silica gel column chromatography to obtain 20 mg of 2-(2-dimercaptopyridyl)ethanol as a yellow-white oily liquid with a yield of 53%.

[0107] 18.7mg (0.1mmol) of 2-(2-dimercaptopyridyl)ethanol was added to a 50mL three-necked round-bottomed flask, 10mL of anhydrous dichloromethane was added, 40mg (0.2mmol) of p-nitrophenyl chloroformate was added, N , N'-diisopropylethylamine 25.9 mg (0.2 mmol), 4-dimethylaminopyridine 1.22 mg (catalytic amount), sti...

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 present invention relates to the field of medicine, in particular to a nucleic acid aptamer drug conjugate and a preparation method and application thereof. The nucleic acid aptamer-drug conjugate provided by the present invention includes a drug molecule group and a nucleic acid aptamer fragment, the drug molecule group is selected from the mitomycin C group, and the drug molecule group and nucleic acid The aptamer fragments are connected by linking groups. The nucleic acid aptamer drug conjugate provided by the present invention not only has all the advantages of nucleic acid aptamers, but also mitomycin C is a non-specific anticancer drug, which has no selectivity for cells. The combination of nucleic acid aptamer and mitomycin C can effectively improve the targeting ability of mitomycin C, thereby achieving the effect of specifically killing tumor cells.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to a nucleic acid aptamer drug conjugate and a preparation method and application thereof. Background technique [0002] Mitomycin is an anti-tumor antibiotic isolated from the culture solution of Streptomyces cephalogeni. It is effective against a variety of solid tumors. It can form cross-links with the double helix structure of DNA, destroy the structure and function of DNA, and inhibit proliferation. The replication of DNA in the proliferative phase has a killing effect on the cells in the proliferative phase, and can also act on the cells in the stationary phase, thereby inhibiting tumor cells. [0003] Aptamer is an oligonucleotide fragment obtained from a nucleic acid molecule library by using an in vitro screening technology-exponential enrichment ligand system evolution technology (Systematic evolution of ligands by exponential enrichment, SELEX). bind to the target molecul...

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
Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K31/407A61P35/00C07H21/00C07H1/00
CPCA61K31/407A61K47/549A61P35/00C07H21/00C07H1/00
Inventor 谭蔚泓王雪强杨秋霞邓正玉王丹何嘉轩谭燕符婷
Owner HUNAN 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