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基于赖氨酸的树枝状聚合物及其“星爆”聚合物衍生物:在DNA压缩和基因构建体体外递送中的应用前景

[Dendrimers based lysine and their "starburst" polymeric derivatives: prospects of use in compacting DNA and in vitro delivery of genetic constructs].

作者信息

Vlasov G P, Korol'kov V I, Pankova G A, Tarasenko I I, Baranov A N, Glazkov P B, Kiselev A V, Ostapenko O V, Lesina E A, Baranov V S

机构信息

Institute of Macromolecular Compounds, Russian Academy of Sciences, Bolshoi pr. 31, St. Petersburg, 199004 Russia.

出版信息

Bioorg Khim. 2004 Jan-Feb;30(1):15-24. doi: 10.1023/b:rubi.0000015768.32255.1a.

Abstract

We attempted to find some compounds for the effective delivery of gene constructs into cells and obtained two trispherical dendrimers on the basis of lysine, (Lys)8-(alpha, epsilon-Lys)4-(alpha, epsilon-Lys)2-(alpha, epsilon-Lys)-Ala-NH2 (D1) and (Lys)8-(alpha, epsilon-Lys)4-(alpha, epsilon-Lys)2-(alpha, epsilon-Lys)-Ala-[Lys(Plm)]2-Ala-NH2 (D2), as well as the starburst polymeric derivatives of D1, (pVIm)8-D1 and (pLys)n-D1, containing poly(N-vinylimidazole) and polylysine chains bound at a single point to the dendrimer amino groups. The conditions of dendrimer-plasmid DNA complex formation were studied. The intracellular localization of these complexes and the expression of gene constructs delivered with their help were analyzed in transfection experiments on the HeLa cell cultures of human epithelial carcinoma and on C2C12 mouse myoblasts. It was found that the chemical structure of dendrimer D1 and its derivatives significantly affected the structure and properties of complex. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.

摘要

我们试图寻找一些能将基因构建体有效递送至细胞的化合物,并基于赖氨酸获得了两种三球形树枝状大分子,即(Lys)8-(α,ε-Lys)4-(α,ε-Lys)2-(α,ε-Lys)-Ala-NH2(D1)和(Lys)8-(α,ε-Lys)4-(α,ε-Lys)2-(α,ε-Lys)-Ala-[Lys(Plm)]2-Ala-NH2(D2),以及D1的星爆型聚合物衍生物,(pVIm)8-D1和(pLys)n-D1,它们含有在单个点与树枝状大分子氨基相连的聚(N-乙烯基咪唑)和聚赖氨酸链。研究了树枝状大分子与质粒DNA复合物形成的条件。在人上皮癌的HeLa细胞培养物和C2C12小鼠成肌细胞的转染实验中,分析了这些复合物的细胞内定位以及借助它们递送的基因构建体的表达情况。发现树枝状大分子D1及其衍生物的化学结构显著影响复合物的结构和性质。论文的英文版本:《俄罗斯生物有机化学杂志》,2004年,第30卷,第1期;另见http://www.maik.ru。

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