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针对高分子量的聚乙烯亚胺(PEI)作为基因载体效率高但毒性大,而低分子量的聚乙烯亚胺虽毒性低但对基因的结合能力差、转染效率低的矛盾,设计合成了主链可生物降解而侧链带有胺类化合物的阳离子聚碳酸酯.首先,2-氨基-1,3-丙二醇和甲基丙烯酰氯反应制得2-(甲基丙烯酰胺基)-1,3-丙二醇,再用氯甲酸乙酯在室温下用三乙胺作碱关环反应得到2-(甲基丙烯酰胺基)三亚甲基碳酸酯(MATC)单体.该单体在二氯甲烷溶液中在1,8-二氮杂二环[5.4.0]十一碳-7-烯(DBU)催化下开环聚合得到聚(2-(甲基丙烯酰胺基)三亚甲基碳酸酯)(PMATC).然后,利用侧基双键和乙二胺或者低分子量PEI的迈克尔加成反应分别制备了带有乙二胺侧基的阳离子聚碳酸酯PTMC-EDA以及带有PEI侧链的聚碳酸酯PTMC-PEI.凝胶色谱(GPC)法测得聚碳酸酯PMATC、阳离子聚碳酸酯PTMC-EDA和PTMC-PEI的重均分子量分别为6300、7400、15100,分子量分布指数分别为1.21、1.83和2.17.这类带有多胺侧基或侧链的阳离子聚碳酸酯在较低用量下即能与pDNA形成表面带正电的粒径200 nm左右的复合物.它们具有与不可降解的25 kDa PEI类似的对pDNA的优良结合能力,并且对细胞的毒性要低得多.
For high molecular weight polyethyleneimine (PEI) as a gene carrier with high efficiency but high toxicity, low molecular weight polyethylenimine has low toxicity but low binding capacity to gene and low transfection efficiency, the design and synthesis of the main First, 2-amino-1,3-propanediol and methacryloyl chloride react to prepare 2- (methacryloylamino) -1,3 - propylene glycol, and then with ethyl chloroformate at room temperature with triethylamine ring-closure reaction to give 2- (methacrylamide) trimethylene carbonate (MATC) monomer. The monomer in methylene chloride solution Was subjected to ring-opening polymerization under 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) catalysis to obtain poly (2- (methacrylamide) trimethylene carbonate) PMATC) .Then, cationic polycarbonate PTMC-EDA with pendant ethylenediamine groups and polycarbonates with PEI side chains were prepared by Michael addition of pendant double bonds to ethylenediamine or low molecular weight PEI The weight average molecular weights of the polycarbonate PMATC, the cationic polycarbonates PTMC-EDA and PTMC-PEI measured by gel permeation chromatography (GPC) were 6300, 7400 and 15100, respectively , Molecular weight distribution index were 1.21,1.83 and 2.17. Such polyamines with side chains or side chains of cationic polycarbonates at lower dosage that can form a positive surface with pDNA composite particle size of about 200 nm They have excellent pDNA binding properties similar to non-degradable 25 kDa PEI and are much less toxic to cells.