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α,β-聚[(N-羟丙基/氨乙基)-DL-天冬酰胺-CO-L-赖氨酸]作为潜在的非病毒性基因载体的研究

α,β-Poly[(N-hydroxypropyl/aminoethyl)-DL-aspartamide-co-L-lysine]:Potential Non-viral Vehicle for Gene Delivery

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【作者】 骆瑛侯思恩高忠明汤谷平

【Author】 Luo Yin~1 Hou Si’en~2 Gao Zhongming~3 Tang Guping~41(Hangzhou First People’s Hospital,Hangzhou 310006,China)2(First Affiliated Hospital of Zhejiang University,Hangzhou 310003,China)3(Zhejiang Xinchang Pharmaceutical Co.Ltd.,Xinchang 312500,China)4(College of Pharmaceutical Science,Zhejiang University,Hangzhou 310006,China)

【机构】 杭州市第一人民医院浙江大学附属第一医院浙江新昌制药厂浙江大学药学院药物所 杭州310006杭州310003新昌312500杭州310006

【摘要】 实验研究了DL-天冬氨酸和L-赖氨酸通过不同的比例合成的一系列聚[DL-天冬氨酸-CO-L-赖氨酸](PAL),经过1H-NMR、FT-IR、X-Ray方法进行表征后确认了结构并证明该类聚合物有较好的规律性。PAL开环后合成α,β-聚[(N-羟丙基/氨乙基)-DL-天冬酰胺-CO-L-赖氨酸](PHAAL),通过对PHAAL在磷酸缓冲液(pH=7.4,0.01M)和酶(木瓜蛋白酶,胰蛋白酶)溶液中降解实验的研究,结果显示该类聚合物具有良好的降解能力。利用MTT方法测PHAAL在Hela,ECV-304,Bcap37细胞中的细胞毒性,实验结果表明PHAAL的细胞毒性较低。利用含溴乙啶(0.25μg/ml)的琼脂糖凝胶(1.0%,w/v)电泳检测PHAAL的DNA结合能力,发现赖氨酸聚合比例高的PHAAL结合DNA的能力较强。综合各种实验结果分析,PHAAL是一类可作为非病毒性基因载体的聚氨基酸类高分子材料。

【Abstract】 A series of Poly[aspartic acid-co-L-lysine](PAL) are copolycondensed by DL-aspartice acid and L-lysine with different ratios.Their constructions are identified by the spectra of ~1H-NMR,FT-IR,X-Ray).These spectra are proved to have good regularity of these copolymers.α,β-Poly[(N-hydroxypropyl/aminoethyl)-DL-Aspartamide-co-L-lysine](PHAAL) is synthesized by ring-opening poly[aspartic acid-co-lysine](PAL).PHAAL has good degradability in the phosphoric acid buffer solution(0.01 M,pH=7.4) in the enzyme solution(Papain,Trypsine).PHAAL appeared tobe low cytotoxicity in Hela,ECV-304,Bcap37 cell lines,which was quantified by MTT assay.The combination ability of PHAAL with plasmid DNA was evaluated by agarose gel electrophoresis with agarose gel(1.0% w/v) containing ethidium bromide(0.25 μg/ml).The PHAAL with higher ratios of lysine in the copolymers have higher ability of condensing DNA.In summary,PHAAL,the polyaminoacid materials, could be one kind of macromolecule materials tobeused as the non-viral gene vehicle.

  • 【文献出处】 生物医学工程学杂志 ,Journal of Biomedical Engineering , 编辑部邮箱 ,2007年01期
  • 【分类号】R346
  • 【被引频次】1
  • 【下载频次】161
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