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

Single-stranded nucleic acid molecule having nitrogen-containing alicyclic skeleton

A single-stranded nucleic acid molecule and backbone technology, applied in the field of single-stranded nucleic acid molecules, can solve problems such as label changes, and achieve the effect of easy synthesis and efficient manufacturing

Active Publication Date: 2013-04-17
BONAC CORP
View PDF14 Cites 20 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, at present, when imparting certain functions and labels to the above-mentioned RNA molecules, for example, only bases, sugar residues, or phosphate groups, which are constituent elements of nucleotide residues, can be modified.
Therefore, in the development of pharmaceuticals and the like using RNA interference, it is extremely difficult to impart further functions or to modify markers while maintaining the function of suppressing gene expression.

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
  • Single-stranded nucleic acid molecule having nitrogen-containing alicyclic skeleton
  • Single-stranded nucleic acid molecule having nitrogen-containing alicyclic skeleton
  • Single-stranded nucleic acid molecule having nitrogen-containing alicyclic skeleton

Examples

Experimental program
Comparison scheme
Effect test

Embodiment A1

[0367] 1. Synthesis of Prolinol

[0368] Prolinol protected with dimethoxytrityl was synthesized according to Scheme 1 shown below.

[0369] [Chemical formula 13]

[0370]

[0371] (1) Fmoc-L-prolinol (compound 2)

[0372] L-prolinol (compound 1) (0.61 g, 6.0 mmol) was dissolved in 70 mL of pure water to prepare an aqueous L-prolinol solution. N-(9-Fluorenemethoxycarbonyl)succinimide (Fmoc-OSu) (2.0 g, 6.0 mmol) was dissolved in 10 mL of THF. This THF solution was added to the above-mentioned L-prolinol aqueous solution, and the mixture was stirred for 1 hour to react both. The reaction solution was separated into a liquid fraction and a precipitate fraction, each fraction was extracted with ethyl acetate, and the organic layers were recovered separately. Then, after combining the respective organic layers, anhydrous sodium sulfate was added to absorb moisture (hereinafter referred to as drying). The above-mentioned organic layer was filtered, the filtrate was recovere...

Embodiment A2

[0405] Next, according to Scheme 3 shown in the following formula, an amidite derivative having L-proline was synthesized.

[0406] [Chemical formula 15]

[0407]

[0408] (1) DMTr-hydroxyamide amino-L-proline (compound 11)

[0409] In an ethanol solution (7 mL) containing DMTr-amide-L-proline (compound 6) (1.00 g, 2.05 mmol) and 5-hydroxyvaleraldehyde (0.33 g, 3.07 mmol), acetic acid was added under ice cooling buffer (7mL). After the mixture was stirred under ice-cooling for 20 minutes, sodium cyanoborohydride (0.77 g, 12.28 mmol) was added, and the mixture was further stirred at room temperature for 7 hours. The above mixed solution was diluted with dichloromethane, washed with water, and further washed with saturated brine. And the above-mentioned organic layer was recovered and dried over sodium sulfate. The above-mentioned organic layer was filtered, and the solvent was distilled off under reduced pressure with respect to the filtrate. The obtained residue was su...

Embodiment A3

[0433] (Example A3) Synthesis of proline diamide amidite

[0434] To generate nucleic acid molecules of the invention comprising linkers having a proline backbone, L-proline diamide amidite and D-proline diamide amidite were synthesized by Scheme 3 above.

[0435] (B3-1) L-proline diamide amidite

[0436] (1) Fmoc-hydroxyamide-L-proline (compound 4)

[0437] Compound 2 (Fmoc-L-proline) of Scheme 3 above was used as the starting material. The above compound 2 (10.00 g, 29.64 mmol), 4-amino-1-butanol (3.18 g, 35.56 mmol) and 1-hydroxybenzotriazole (10.90 g, 70.72 mmol) were mixed, and the above mixture was added under reduced pressure. Under degassing, filled with argon. Anhydrous acetonitrile (140 mL) was added to the above mixture at room temperature, followed by addition of an anhydrous acetonitrile solution (70 mL) of dicyclohexylcarbodiimide (7.34 g, 35.56 mmol), followed by stirring at room temperature for 15 minutes under an argon atmosphere. Hour. After completion o...

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 purpose of the present invention is to provide a novel nucleic acid molecule which can be easily and efficiently produced and is capable of inhibiting the expression of a gene. A single-stranded nucleic acid molecule which contains an expression inhibitory sequence, said expression inhibitory sequence being capable of inhibiting the expression of a target gene, and comprises a region (X), a linker region (Lx) and a region (Xc), characterized in that: the linker region (Lx) is linked between the region (X) and the region (Xc); the region (Xc) is complementary to the region (X); the region (X) and / or the region (Xc) contain said expression inhibitory sequence; and the linker region (Lx) has a non-nucleotide structure containing a pyrrolidine skeleton and / or a piperidine skeleton. This single-stranded nucleic acid molecule can inhibit the expression of the aforesaid target gene.

Description

technical field [0001] The present invention relates to a single-stranded nucleic acid molecule for inhibiting gene expression, and more specifically, to a single-stranded nucleic acid molecule having a nitrogen-containing alicyclic backbone, a composition comprising the single-stranded nucleic acid molecule, and uses thereof. Background technique [0002] As a technique for suppressing gene expression, for example, RNA interference (RNAi) is known (Non-Patent Document 1). Inhibition of gene expression by RNA interference is generally carried out by administering, for example, a short double-stranded RNA molecule in a cell or the like. The above-mentioned double-stranded RNA molecules are generally referred to as siRNA (Small Interfering RNA). In addition, a circular RNA molecule that partially forms a double strand by intramolecular annealing has also been reported, and gene expression can also be inhibited by this RNA molecule (Patent Document 1). However, in these metho...

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): C12N15/113C07D207/08
CPCA61P29/00A61P43/00C12N15/113C12N2310/11C12N2310/14C12N2310/3519C12N2310/531C12N2330/30C12N2320/51C07D207/08C07H21/00
Inventor 大木忠明林宏刚白水久男滨崎智洋伊藤彰浩铃木宽
Owner BONAC CORP
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