Poly(methyl)acrylamide cationic polymer modified by natural arginine on side chain, preparation method and application

A technology of acrylamide cationic polymers, applied in the field of poly(meth)acrylamide cationic polymers and gene delivery carriers, can solve the problem of low transfection efficiency

Inactive Publication Date: 2013-10-23
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] The transfection efficiency of cationic polymers as gene carriers is relatively low, because there are various obstacles in the process of gene transfection, among which the cell membrane and nuclear membrane are the two major obstacles that cationic polymer carriers need to overcome, and they also affect Important factor for its transfection efficiency

Method used

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  • Poly(methyl)acrylamide cationic polymer modified by natural arginine on side chain, preparation method and application
  • Poly(methyl)acrylamide cationic polymer modified by natural arginine on side chain, preparation method and application
  • Poly(methyl)acrylamide cationic polymer modified by natural arginine on side chain, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] The first step: Add 0.26g (2.2mmol) 1,6‐hexanediamine and 0.48g (2.2mmol) di-tert-butyl dicarbonate, 0.5ml triethylamine, 25ml methanol into the reaction flask, at 20°C The reaction was stirred for 20 min. The solvent methanol was removed by rotary evaporation under reduced pressure, and 10ml of 1M NaH 2 PO 4 The solution dissolves the residue, and washes twice with 15 ml of ether. Then adjust the pH value of the aqueous phase to above 9 with 1M NaOH solution, extract 4 times with 15 ml of ethyl acetate, combine the organic phases, and dry with anhydrous sodium sulfate. Finally, the solvent was removed by rotary evaporation under reduced pressure and purified to obtain hexamethylenediamine protected by a single-terminal amino Boc in a transparent oil with a yield of 35%. Its main chemical structural features are as follows:

[0042] 1 H NMR (CDCl 3 ):3.11(‐CH 2 NHBoc), 2.67(‐CH 2 NH 2 ), 1.55‐1.27 (4×CH 2 ,C(CH 3 ) 3 )

[0043] The second step: Fully dissolv...

Embodiment 2

[0054] tert-butoxycarbonyl‐N ω ‐(2,2,4,6,7‐pentamethyldihydrobenzofuran‐5‐sulfonyl)‐L‐arginine (Boc‐Arg(Pbf)‐OH 354 mg), benzotriazole‐N ,N,N',N'-Tetramethyluronium hexafluorophosphate (HBTU254mg), diisopropylethylamine (DIPEA160μL) were dissolved in 15ml DMF solution, stirred and reacted at 20°C for 30min, and added to Example 1 The four-step reaction obtained 250 mg of acrylamide polymer product with a degree of polymerization of 28 and containing side group terminal amino functional groups, and continued to stir and react at 20° C. for 3 days. The organic solvent was removed by rotary evaporation under reduced pressure, a mixture of 5 ml of dichloromethane and 5 ml of trifluoroacetic acid was added, and the reaction was stirred at 20° C. for 1 h. Then remove the organic solvent under reduced pressure, then add 25ml of water to mix and filter, dialyze the resulting filtrate in pure water for 2 days, and further freeze-dry to obtain the polyacrylamide cationic functional pol...

Embodiment 3

[0059] The acryloyl chloride in Example 1 was changed to methacryloyl chloride, and the same reaction conditions and preparation steps as in Example 1 were maintained to synthesize the obtained hexamethylenediamine single-terminal amino Boc-protected methacrylamide polymer. pass 1 H nuclear magnetic resonance compares the characteristic peak integral of RAFT reagent and the characteristic peak integral of monomer, calculates that its degree of polymerization is 33, and its number average molecular weight is M n,NMR =9.7KDa. The number molecular weight was measured by gel permeation chromatography (GPC) with tetrahydrofuran as the mobile phase. n,GPC =10.7KDa, PDI is 1.16. Further, the obtained polymer product was dissolved in a mixture of 5 ml of dichloromethane and 0.5 ml of hydrochloric acid, stirred for 1 h, concentrated by rotary evaporation under reduced pressure, precipitated in glacial ether, filtered, and dried in a vacuum oven to prepare A methacrylamide polymer co...

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Abstract

The invention discloses a poly(methyl)acrylamide cationic polymer modified by natural arginine on a side chain, a preparation method and an application. The (methyl)acrylamide polymer with tert-butyloxycarbonyl (Boc) protected amino group on the side chain is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization; arginine containing a protection group is linked to a poly(methyl)acrylamide molecule by using the amino group with the protection group on the side chain removed; and the cationic functional polymer is obtained after the protection group is removed. The preparation method is simple and mild in conditions. The poly(methyl)acrylamide cationic polymer modified by natural arginine on the side chain has low cytotoxicity and high biocompatibility, can combine genes efficiently, has high gene transfection efficiency, is an effective non-viral gene vector, and is used for in-vitro gene transfection reagent.

Description

technical field [0001] The invention belongs to the field of non-viral gene carriers, and in particular relates to a poly(meth)acrylamide cationic polymer modified by side group natural arginine, a preparation method and its use as a gene delivery carrier. Background technique [0002] Gene therapy (Gene Therapy) is the introduction of gene fragments with certain therapeutic effects into target cells for expression through certain means, so as to correct or compensate for the defects or abnormalities of disease-causing genes and achieve the purpose of disease treatment. Compared with traditional drug therapy, gene therapy can fundamentally control the disease. At present, due to the lack of safe, efficient and practical gene carriers, the practical application of gene therapy has been greatly restricted. Generally, gene carrier materials can be divided into viral vectors and non-viral vectors according to their sources. Viral vectors generally have high gene transfection ef...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F120/60C08F8/32C08F8/00C08F2/38C12N15/87C12N15/85
Inventor 曹阿民李慧罗挺盛瑞隆
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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