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Delta-valerolactone-based polymer and preparation method and application thereof

A technology of valerolactone and polymer, applied in the field of delta-valerolactone-based polymer and its preparation, can solve problems such as high toxicity and low transfection efficiency, and achieve easy control, simple preparation method and good compatibility sexual effect

Active Publication Date: 2017-09-01
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, non-viral gene vectors also have some problems to be solved, that is, the transfection efficiency is lower than that of viral gene vectors, and the toxicity is relatively high

Method used

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  • Delta-valerolactone-based polymer and preparation method and application thereof
  • Delta-valerolactone-based polymer and preparation method and application thereof
  • Delta-valerolactone-based polymer and preparation method and application thereof

Examples

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example 1

[0051] A delta-valerolactone-based polymer characterized in that the delta-valerolactone-based polymer has the structure in [Chemical Formula 1] shown below:

[0052] [chemical formula 1]

[0053]

[0054] Among them, R 2 for and One of them, n is greater than or equal to 1, and m is greater than or equal to 0. n and m are varied according to the ratio of the two parts.

[0055] [Chemical formula 1] The specific synthetic route of the polymer is:

[0056]

[0057] Wherein, the compound of [chemical formula 2] is compound 1 in the synthetic route, and in the compound of [chemical formula 3], a is 2, 6, 10 or 14, and the corresponding compounds in the synthetic route are 2, 3, 4, 5;

[0058] The obtained δ-valerolactone-based polymer has a number-average molecular mass in the range of 2,000-10,000, and the structural terminal is a hydroxyl group.

[0059] Concrete synthetic steps are as follows:

[0060] Step 1. Weigh the exocyclic α, β-unsaturated δ-valerolactone...

example 2

[0075] Prepare solutions of different concentrations of polymers (B1-B6, C1-C4, P1) respectively, place the solutions of different concentrations of polymers and PGL-3 plasmid DNA (9μg / mL) in a water bath at 37°C for 1 hour, and carry out DNA agarose gel retardation experiment obtained the gel retardation results of different concentrations of polymers (B1-B6, C1-C4, P1) on PGL-3DNA.

[0076] figure 1 a~1k are the agarose gel retardation experiment results of the PGL-3DNA of the polymers B1-B6, C1-C4, and P1 of the present invention respectively; wherein, figure 1 a is the agarose gel retardation experiment diagram of polymer B1 to pGL-3 in Example 1 of the present invention; figure 1 b is the agarose gel retardation experiment diagram of polymer B2 to pGL-3 in Example 1 of the present invention; figure 1 c is the agarose gel retardation experiment diagram of polymer B3 to pGL-3 in Example 1 of the present invention; figure 1 d is the agarose gel retardation experiment diag...

example 3

[0079] Prepare solutions of different concentrations of polymers (B1-B6, C1-C4, P1), put the solutions of different concentrations of polymers and PGL-3 plasmid DNA (9μg / mL) in a water bath at 37°C for 1 hour, and carry out In the study of dynamic laser light scattering technology, we studied the particle size of the aggregated polymer and DNA.

[0080] figure 2 a~2k are the dynamic light scattering experiment results of PGL-3DNA of polymers B1-B6, C1-C4, and P1 of the present invention, respectively; figure 2 a is a dynamic light scattering particle size diagram of a complex of polymer B1 and plasmid DNA according to the present invention; figure 2 B is the dynamic light scattering particle size diagram of the complex of polymer B2 and plasmid DNA according to the present invention; figure 2 c is the dynamic light scattering particle size diagram of the complex of polymer B3 and plasmid DNA according to the present invention; figure 2 D is the dynamic light scattering...

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Abstract

The invention provides a delta-valerolactone-based polymer. The structure of the delta-valerolactone-based polymer is subjected to infrared, nuclear magnetism and gel permeation chromatography characterization. The invention further discloses a preparation method and application of the delta-valerolactone-based polymer. The delta-valerolactone-based polymer is prepared through a Click reaction and a ring-opening polymerization, the reaction is simple and convenient, and the yield is high. The delta-valerolactone-based polymer is degradable under a certain condition, and acts with nucleic acid to form nano-particles easy to adsorb by cells; green fluorescent protein (GFP) and luciferase (Luciferase) expression experiments testify that the polymer can serve as a degradable non-viral gene vector and has high transfection efficiency; and the preparation method of the polymer and a preparation method of a transgenic vector are simple, mature and easy to learn.

Description

technical field [0001] The invention belongs to the technical field of gene carriers, and in particular relates to a delta-valerolactone-based polymer that can be used as a non-viral gene carrier and its preparation method and application. Background technique [0002] Gene therapy is to introduce exogenous 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 can effectively bring extracellular nucleic acid into the cell, and can protect the nucleic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G63/688C08G63/87C08G63/78C12N15/87
CPCC08G63/6882C08G63/78C08G63/823C08G63/87C12N15/87
Inventor 卢忠林宋玲丁爱祥何兰龚兵
Owner BEIJING NORMAL UNIVERSITY
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