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

Compound, nucleic acid compound molecules and nucleic acid complex as well as preparation methods and application thereof

A compound and reaction technology, which is applied in the field of preparation of small interfering nucleic acid drugs, can solve the problems that safety indicators such as toxicity cannot be fully trusted, and the proportion is small, and achieve the effects of reducing toxicity, reducing dosage, and improving tissue specificity

Active Publication Date: 2013-05-29
KUNSHAN RNAI INST
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In the currently reported technology, in the siRNA complex molecules constructed for drug administration, the proportion of siRNA with medicinal effect is very small, and the auxiliary medium occupies a large mass ratio, and the safety indicators such as the toxicity of these mediums cannot be completely determined. trust

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
  • Compound, nucleic acid compound molecules and nucleic acid complex as well as preparation methods and application thereof
  • Compound, nucleic acid compound molecules and nucleic acid complex as well as preparation methods and application thereof
  • Compound, nucleic acid compound molecules and nucleic acid complex as well as preparation methods and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0039] According to a preferred embodiment of the present invention, the compound has a structure represented by formula V,

[0040] Formula V,

[0041] Wherein, B is selected from N, P=O, C-X 5 -A 5 or C-R 8 ;A 1 、A 2 、A 3 、A 4 and A 5 Each independently is a group shown in formula I or a group shown in formula II; X 1 、X 2 、X 3 、X 4 and x 5 Each independently is an optionally substituted C1-C20 alkylene group or a group represented by formula III;

[0042] Formula III,

[0043] Among them, R 6 and R 37 is a bond or an optionally substituted C1-C14 alkylene group;

[0044] R 7 is an optionally substituted C1-C20 hydrocarbyl or targeting group; R 8 is H, an optionally substituted C1-C20 hydrocarbon group or a targeting group.

[0045] In the present invention, the three or more first connection structures are the basis for the compound to be used as a carrier to form a spatial topology, and the three or more are preferably 3-6, such as 3, 4, 5 or 6 ...

Embodiment 1

[0225] This example is used to illustrate the synthesis of the central molecule

[0226] (1) Compound (2Z, 2′Z, 2″Z)-4,4′, 4″-(2,2′, 2″-nitrilo three (ethane-2,1 Synthesis of -diyl)tri(azanediyl))tri(4-carbonylbut-2-enoic acid)

[0227]

[0228] Add compound (1) (13.38mmol, 2.016g) into a dry 500mL round bottom flask, then add 200mL of anhydrous dichloromethane, stir evenly with electromagnetic. Add maleic anhydride (45.16mmol, 4.435g) into the round bottom flask, increase the stirring speed, and heat to reflux at 50°C for 2h. The solvent dichloromethane was removed by rotary evaporation to obtain 4.984 g of compound (4) as a yellow solid with a yield of 83%.

[0229] (2) Compound 1,1',1"-(2,2',2"-nitrilotri(ethane-2,1-diyl))tri(1H-pyrrole-2 , 5-diketone) synthesis

[0230]

[0231] Add compound (4) (5mmol, 2.204g), triethylamine (4.158mmol, 420mg), sodium acetate (4.085mmol, 335mg) respectively into a dry 100mL round bottom flask, then add 10mL of acetone, and stir...

Embodiment 2

[0234] This embodiment is used to illustrate the preparation of the nucleic acid complex molecule N1 of the present invention

[0235] Dissolve the terminal sulfhydryl-modified oligonucleotide R1 in 100 microliters of RNase-free water, add Tri-HCl buffer (pH=8.0, final concentration is 20mM), the final concentration of R1 is 1mM, and mix well; 0.11 mM compound (5), placed in a flowing high-purity argon atmosphere for 5 min, and incubated at 45° C. for 2 h. Repeat the above steps of adding compound (5) and argon protection and reacting for 2 h twice. Afterwards, polyacrylamide (6% urea) electrophoresis and gel purification were carried out, and a single band corresponding to the position of the 90nt natural oligonucleotide was cut out for gel elution. After 2 hours, it was washed with 0.3M sodium acetate and 75% ethanol precipitation. Dehydration for 1h. Centrifuge at 13000 rpm for 15 min at 4°C, discard the supernatant to obtain N1.

[0236] N1 was detected by 6% and 15% po...

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

PropertyMeasurementUnit
Diameteraaaaaaaaaa
Login to View More

Abstract

The invention discloses a compound and a preparation method thereof and also provides nucleic acid compound molecules and a preparation method thereof, a preparation method of a nucleic acid complex and the nucleic acid complex prepared by the method. The preparation method of the compound comprises a step of contacting the nucleic acid compound molecules containing first chain nucleic acid with the nucleic acid compound molecules containing second chain nucleic acid, and annealing the nucleic acid compound molecules, wherein at least part of the first chain nucleic acid and at least part of the second chain nucleic acid have complementary capacities under a stringent condition. Moreover, the invention also provides applications of the compound, the nucleic acid compound molecules and the nucleic acid complex in preparation of a small-interfering nucleic acid medicament. Through a novel spatial topology manner, the nucleic acid complex having a property of assisting penetration of cell membranes for the small-interfering nucleic acid medicament is formed, is enhanced in stability and facilitates the release of the small-interfering nucleic acid medicament; and in addition, the ratio of the small-interfering nucleic acid medicament in the nucleic acid complex is high, so that the nucleic acid complex is safer and more reliable and has economic advantages.

Description

technical field [0001] The present invention relates to a compound, a nucleic acid complex molecule and a nucleic acid complex, the preparation method of the compound, the nucleic acid complex molecule and the nucleic acid complex, and the use of the compound, the nucleic acid complex molecule and the nucleic acid complex in preparing small interfering nucleic acid drugs in the application. Background technique [0002] RNA interference (RNA interference, RNAi) is a process in which double-stranded RNA (double-stranded RNA, dsRNA) molecules shut down the expression of the corresponding gene or silence the gene at the mRNA level. RNA interference technology, also known as gene knockdown (knock-down) or gene silencing (gene silencing), is a typical post-transcriptional gene regulation method, also known as post-transcriptional gene silencing (PTGS). ). It was first elucidated by Fire and Mello in Caenorhabditis elegans (A.Fire, S.Xu, M.K.Montgomery, S.A.Kostas, S.E.Driver, C...

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): C07C233/38C07C231/02C07C231/12C07D207/452C07H21/00C07H1/00C07C229/08C07C227/18C07C227/20C07K16/00C07K5/083C12N15/115C12N15/113C12N15/10A61K48/00
CPCC12N15/115A61K48/00C07C231/12C07C227/20C07C229/08C07K16/00C12N15/10C07C233/38C12Q1/6811C12N15/111C12N15/113C12N2310/11C07D207/452C07C227/18C12N2320/32C12N2310/14C07H21/00C07C231/02C07H1/00C12N2310/52
Inventor 席真章骏斌魏绿
Owner KUNSHAN RNAI INST
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