Cation functional polymers with natural amino acid as side group, preparation method and application of polymer

Abstract

The invention relates to a class of cation functional polymers with natural amino acid as a side group, and a preparation method and an application of the polymer. A series of water-soluble cation functional polymers with amino acid side groups is prepared by performing controllable polymerization on Boc-amino acid functionalized acrylate monomers through reversible addition-fragmentation chain transfer polymerization reaction, and removing the Boc protecting groups. The preparation method has the advantages that the operation is simple and convenient, the cost is low, polymer structure is regular, molecular weight distribution is narrow, raw materials are easy to obtain and the like. The class of water-soluble cation functional polymers with amino acid side groups is formed by taking natural amino acid as important building blocks, presents very low cytotoxicity by reference to commercial linear polylysine PLL (15-30K) and branched polyethyleneimine bPEI-25K in multiple cell lineages, present high-efficiency gene transfection in multiple cell strains when being used as a cation gene vector material, and has a good prospect in the low-toxicity and high-efficiency cation polymer gene vector application field.

Description

technical field [0001] The invention relates to the field of biofunctional materials. It specifically relates to a method for preparing a series of cationic functional polymers with natural amino acids as side groups by reversible addition-fragmentation chain transfer polymerization (RAFT) reaction and its application as a biological functional carrier material. Background technique [0002] Gene therapy refers to the introduction of exogenous functional therapeutic gene drugs into diseased cells or tissues through a suitable carrier, through intracellular integration and functional expression, to correct or compensate diseases caused by gene defects and abnormalities, and achieve therapeutic purposes. With the development of today's molecular biology technology and the rapid progress of the Human Genome Project, people have studied the molecular biological origin of many important congenital acquired genetic diseases, and found that new biomedical treatments can be develope...

AI Technical Summary

Problems solved by technology

In recent years, dendritic macromolecules (such as dendritic polylysine) have been extensively studied in the application of gene carriers. The macromolecular structure is regular and the molecular weight distribution is narrow. Acid dendritic functional macromolecule) as a gene carrier shows good transfection efficiency, and the efficiency of gene transfection in living cells can be further increased with the increase of dendritic macromolecule generation, but at the same time, it is accompanied by obvious cytotoxicity, which limits its practicality. application

At the same time, functional macromolecules with a dendritic structure generally need to be prepared by repeated steps of functional group protection, coupling, purification and separation, and functional group deprotection. High cost, not suitable for large-scale preparation and application

On the other hand, catalyzed ring-opening polymerization (J. Polym. Sci., Part A: Polym. Chem 2000; 38: 3011-3018) of amino acid benzyl ester anhydride (NCA) functional monomers can be prepared with linear structure Polyamino acid cationic functional macromolecules (such as polylysine PLL, polyarginine, polyhistidine, etc.), but the above-mentioned ring-opening polymerization reaction needs to be carried out under harsh conditions of anhydrous and oxygen, and the prepared The molecular weight distribution of the polymer product is wide, and the regularity of the macromolecular structure is poor

In order to further develop new methods for the synthesis of dendrimers and linear polymers based on natural amino acids, Sanda. 1999; 200: 2651-2661), at the same time, Gao et al. used atom transfer radical polymerization (ATRP) to prepare functional polymers coupled with various amino acid side groups (Biomacromolecu les 2010; 11: 3609-3616), but The above polymerization method fails to realize the construction of new cationic functional polymers with monodisperse molecular weight from natural amino acids, and the metal catalyst used in the ATRP preparation method is likely to cause trace metal ions to remain, which is not conducive to its application as a biofunctional material

So far, there is no research report on functional macromolecules with amino acid side groups derived from amino acids synthesized and prepared based on the above two methods as gene carriers.

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