Tetravinyl-based Gemini type amphiphilic compound as well as preparation method and application thereof

An amphiphilic compound, tetravinyl technology, applied in the field of Gemini-type amphiphilic compounds, can solve the problems of great difference in transfection efficiency and single function

Active Publication Date: 2017-02-22
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, their transfection efficiency is still far from that of viral vectors, and the reported Gemini vectors have a single function, which is only used as a DNA condensation and transportation tool

Method used

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  • Tetravinyl-based Gemini type amphiphilic compound as well as preparation method and application thereof
  • Tetravinyl-based Gemini type amphiphilic compound as well as preparation method and application thereof
  • Tetravinyl-based Gemini type amphiphilic compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] The Gemini type amphiphilic compound based on tetravinyl shown in synthetic formula (I),

[0084]

[0085] R represents straight-chain alkyl or straight-chain monoalkenyl; In this embodiment, R represents C 8 、C 12 and C 18 straight chain alkyl, and (E)-9-octadecenyl as an example; R represents C 8 When it is a straight chain alkyl group, it is compound 1, and R represents C 12 When it is a straight chain alkyl group, it is compound 2, and R represents C 18 It is compound 3 when straight-chain alkyl, and compound 4 when R represents (E)-9-octadecenyl.

[0086] The synthetic route is:

[0087]

[0088] The preparation process of route 1 compounds 1, 2, 3 and 4: (i) zinc powder, titanium tetrachloride, tetrahydrofuran, -78 ° C to 60 ° C, overnight; (ii) potassium carbonate, potassium iodide, acetone, reflux, 48 hours ; (iii) n-butyllithium, THF, -78°C to room temperature; (iv) a: copper sulfate pentahydrate, sodium ascorbate, THF / water, argon, room temperature...

Embodiment 2

[0111] Compounds 1, 2, 3 and 4 were configured into aqueous solutions of different concentrations, and the fluorescence intensity of the aqueous solutions of compounds 1 to 4 was measured; the maximum value of the fluorescence intensity varied with the concentration (10 -9 -10 -3 M) change trend plotting, get Figure 1A ~ Figure 1D ,exist Figure 1A-1D In , the X-axis is the solution concentration, and the Y-axis is the fluorescence intensity.

[0112] Figure 1A-1D They are the determination charts of critical micelle concentration and micelle morphology of compounds 1-4, respectively. Figure 1A-1D It can be seen that the critical micelle concentrations of compounds 1 to 4 are all very low, and the critical micelle concentrations of compounds 1 to 4 are 4.62×10 - 6 M, 4.58×10 -6 M, 4.02×10 -6 M and 4.94×10 -6 M.

[0113] Take 2 μL of the aqueous solution of mixture 1 to 4 with a concentration of 5 μM, drop them on a 200-mesh copper grid, and dry them naturally. Fi...

Embodiment 3

[0116] Solutions of compounds 1-4 with different concentrations were prepared respectively, and the solutions of compounds 1-4 with different concentrations and pUC18 plasmid DNA (9 μg / mL) were placed in a 37°C water bath for 1 hour, and the DNA agarose gel retardation experiment was carried out to obtain Gel retardation results of pUC18 DNA with different concentrations of compounds 1-4.

[0117] Figure 2A-2D Respectively, the results of the agarose gel retardation experiment of the pUC18 DNA of compounds 1-4 of the present invention; Figure 2A-2D The value marked above is the test concentration (μM); Figure 2A-2D It shows that compounds 1-4 can completely block the migration of DNA in agarose at lower concentrations; the lowest blocking concentrations of compounds 1-4 are: 16 μM, 16 μM, 12 μM and 30 μM, respectively.

[0118] It can be concluded from Example 2 that the tetravinyl-based Gemini amphiphilic compound prepared by the present invention has good self-assembly ...

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Abstract

The invention discloses a tetravinyl-based Gemini type amphiphilic compound as well as a preparation method and application thereof. The compound disclosed by the invention is mainly prepared through McMurry coupling reaction, nucleophilic substitution reaction and Click reaction; the structure of the compound is also confirmed through infrared, nuclear magnetic and mass-spectrum ways; in an aqueous solution, molecules of a derivative of the compound disclosed by the invention self-assemble to form aggregation-induced fluorescence-enhanced micelles (AIE micelles); the compound acts with a nucleic acid, and then can co-aggregate to form nano particles easy for cellular uptake; green fluorescent protein (GFP) and luciferase (Luciferase) expression assays prove that the compound self and a liposome formed with dioleoyl phosphatidyl ethanolamine (DOPE) can be used as non-viral gene vectors; meanwhile, the derivative is successfully used for tracing the cellular uptake and release processes of pGL-3 and FAM-DNA by utilizing the reversible transformation between the self-assembly of the compound and the co-assembly with DNA (Deoxyribonucleic Acid).

Description

technical field [0001] The present invention relates to a tetravinyl-based Gemini-type amphiphilic compound, in particular to the preparation of a tetraphenylethenyl-based Gemini-type amphiphilic compound and its use as a non-viral gene carrier and DNA molecular fluorescent probe , biological imaging agents and gene tracers. Background technique [0002] Gene therapy is to introduce foreign aid normal genes into diseased cells to replace or repair defective genes, so as to achieve the purpose of treating corresponding diseases. There are many negatively charged glycoproteins and glycolipid compounds on the cell membrane, and the phosphate groups in the nucleic acid skeleton structure are also negatively charged, and the nucleic acid itself has a large volume, so the naked nucleic acid is difficult to be phagocytized by cells. In order to solve the problem that naked nucleic acid is difficult to be taken up by cells, researchers have developed gene carriers. Gene carrier ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/14C09K9/02C09K11/06G01N21/64C12N15/87
CPCC07D403/14C09K9/02C09K11/06C12N15/87G01N21/6428
Inventor 卢忠林何兰丁爱祥谭筝丽
Owner BEIJING NORMAL UNIVERSITY
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