5'-amino-2',5'-dideoxynucleotide phospholipid molecules, and preparation method and application thereof

A technology of deoxynucleotide phospholipids and deoxynucleoside phospholipids, which is applied in the field of new biomaterials, can solve the problems of difficult effective release, high cytotoxicity and serum toxicity of cationic liposomes, and achieves good efficacy, simple and efficient synthesis method, and preparation simple effect

Active Publication Date: 2013-08-07
PEKING UNIV
View PDF3 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because the surface of the cell membrane is negatively charged, and serum also contains a large number of electronegative proteins, cationic liposomes have high cytotoxicity an

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
  • 5'-amino-2',5'-dideoxynucleotide phospholipid molecules, and preparation method and application thereof
  • 5'-amino-2',5'-dideoxynucleotide phospholipid molecules, and preparation method and application thereof
  • 5'-amino-2',5'-dideoxynucleotide phospholipid molecules, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0066] [Example 1] Synthesis of 5'-p-methylbenzenesulfonyl thymidine

[0067] Thymidine (24.2 g, 0.1 mol) was dissolved in anhydrous pyridine (200 mL), and the temperature was cooled to 0 °C in an ice bath. p-Toluenesulfonyl chloride (23 g, 0.12 mol) was dissolved in anhydrous pyridine (100 mL), and slowly added dropwise to the aforementioned reaction solution through a micro injector, and the dropwise addition process continued for 6 h. The reaction process was always carried out at 0 °C under the protection of argon. After the dropwise addition, the reaction was returned to room temperature, and stirring was continued for 6 h. Pyridine was evaporated under reduced pressure. To the residue was added 500 mL of ethyl acetate and NaHCO 3 Aqueous solution (10%) 300 mL, a large amount of white solid was precipitated. Filtration, the obtained white solid is the target product. The filtrate was collected, the organic phase was separated, and then the aqueous phase was washed wi...

Example Embodiment

[0068] [Example 2] Synthesis of 5'-azido-2',5'-dideoxythymidine

[0069] 5'-p-methylbenzyl thymidine (5 g, 12.6 mmol) was dissolved in dry DMF (25 mL), to which was added NaN 3 (1.2g, 19mmol), heated to 70°C, and reacted under argon protection for 12h. The solvent was evaporated under reduced pressure. To the residue was added dichloromethane (50 mL), followed by washing with water (30 mL). Anhydrous Na for organic phase 2 SO 4Dry and separate by silica gel column chromatography, eluent DCM:MeOH=20:1, to obtain 2.9 g of the target product (yield 85%). white solid. 1 H NMR (400MHz, DMSO-d 6 ):δ=11.31(s,1H),7.49(s,1H),6.20(t,J=7.2Hz,1H),5.39(d,J=4.0Hz,1H),4.20(s,1H),3.79 -3.85(m,1H),3.56(d,J=5.2Hz,2H),2.20-2.30(m,1H),2.05-2.15(m,1H),1.79(s,3H); 13 C NMR (100MHz, DMSO-d 6 ):δ=163.7, 150.5, 136.1, 109.8, 84.6, 83.9, 70.7, 51.6, 38.1, 12.1; 1298.8, 1272.8, 1067.3, 963.4, 856.2, 636.4, 553.4, 493.8cm -1 ;MS(ESI-TOF+)for C 10 h 13 N 5 o 4 Na[M+Na] + found 290.1042,cal...

Example Embodiment

[0070] [Example 3] Synthesis of 5'-amino-2',5'-dideoxythymidine

[0071] Take 5'-azido-2',5'-dideoxythymidine (5.5g, 20mmol) and dissolve it in methanol (150mL), add 10% palladium carbon catalyst (0.55g), and place it in a hydrogenation apparatus hydrogenation. The pressure is 60Psi. After hydrogenation at room temperature for 5 h, the reaction was stopped. TLC detection found that the raw material had reacted completely. Suction filtration through celite under reduced pressure to remove the solid matter, and the obtained filtrate was evaporated to dryness to obtain 4.8 g of light yellow solid. The solid is insoluble in organic solvents such as methanol and ethyl acetate, and is very polar, and cannot be separated by ordinary silica gel column chromatography. The resulting solid was dissolved in water and purified by Dowex 50, a strongly acidic ion exchange resin, to obtain 4.7 g of the target product with a yield of 95%. white solid. 1 H NMR (400MHz, DMSO-d 6 ):δ=7.65(...

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
Granularityaaaaaaaaaa
Diameteraaaaaaaaaa
Diameteraaaaaaaaaa
Login to view more

Abstract

The invention discloses 5'-amino-2',5'-dideoxynucleotide phospholipid molecules, and a preparation method and an application thereof. The 5'-amino-2',5'-dideoxynucleotide phospholipid molecules provided by the invention have an amphiphilic structure represented by the formula (I). 5'-amino-2',5'-dideoxynucleoside is adopted as a hydrophilic head, and glycerol fatty ether connected by using a phosphate bond is adopted as a hydrophobic tail, such that an amphiphilic molecule is formed. The Base group is common purine and pyrimidine bases, and R group is saturated or unsaturated aliphatic carbon chain. In a water-phase solvent, the dideoxynucleotide phospholipid molecule can form a plurality of supramolecular structures including multi-layer film structure, lipid structure, fibrous structure, and hydrogel. Therefore, 5'-amino-2',5'-dideoxynucleotide phospholipid molecules have certain potential to be used as aggregation, trapping, loading, or carrying type nucleic acid medicines, and can be used as a high-efficiency biological material for mediating transmembrane of nucleic acid medicines.

Description

technical field [0001] The invention relates to a series of 5'-amino-2', 5'-dideoxynucleotide phospholipid molecules and a chemical synthesis method thereof, as well as the series of 5'-amino-2', 5'-dideoxynucleotides The supramolecular structure formed by the self-assembly of phospholipid molecules in an aqueous solvent. It belongs to the field of new biological materials. Background technique [0002] The introduction of double-stranded RNA (siRNA, small interfering RNA) composed of sense RNA and antisense RNA corresponding to mRNA into cells can induce specific degradation of mRNA, resulting in corresponding gene silencing. This sequence-specific post-transcriptional gene silencing mechanism is called RNA interference (RNAi). As a potential drug, siRNA will open up a new path for the treatment of human diseases. But the in vivo transport of siRNA is also problematic. For example, its serum stability is not good, and it is easily degraded by RNase in serum; after overa...

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): C07H19/10C07H1/00C12N15/87
Inventor 杨振军潘德林关注张礼和
Owner PEKING UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap