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PVP两亲性嵌段共聚物对超螺旋DNA的裂解活性

         

摘要

以PVP-Cl为大分子引发剂,经ATRP聚合制备得到窄分子量分布、结构可控的含不同亲水/疏水比例的两亲性聚N-乙烯基吡咯烷酮-b-聚N-甲基丙烯酰基-N'-Boc-色氨酸酰胺基硫脲嵌段共聚物(PVP-b-PTrpAMT-I,II,III).1H NMR核磁共振、GPC-MALLS以及凝胶电泳对嵌段共聚物的结构进行了表征、对超螺旋质粒DNA的裂解行为进行了研究.结果表明PVP-b-PTrpAMT可以显著诱导超螺旋质粒DNA裂解,使超螺旋型DNA转变为缺口型,而缺口型DNA在基因转染过程中可有效避免其在细胞内被降解,提高转染效率.该嵌段共聚物对DNA的裂解活性与疏水链段含量、共聚物与DNA的质量比以及与DNA的共孵育时间有关.%Amphiphilic block copolymers poly(N-vinylpyrrolidone)-block-poly(N-t-Boc-tryptophanamido-N'-methacryl thiourea)(PVP-b-PTrpAMT-I,II,III) were designed and synthesized with well defined structures by atom transfer radical polymerization(ATRP) using PVP-Cl as macroinitiator.The chemical structures of the block copolymers were characterized by 1H NMR and GPC-MALLS.Agarose gel electrophoresis study demonstrated that PVP-b-PTrpAMT can induce and cleavage supercoiled DNA into nicked DNA.The nicked DNA can avoid the degradation of DNA in the cell efficiently and have a potential ability to enhance the gene transfection.The cleavage activity of these block copolymers was obviously dependent on the different composition of the copolymer,quality ratio of the copolymer with plasmid DNA and the incubating time together with plasmid DNA.

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