Structural effects of carbohydrate-containing polycations on gene delivery. 2. Charge center type
Structural effects of carbohydrate-containing polycations on gene delivery. 2. Charge center type
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DOI：
10.1021/bc025593c
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发表时间：
2003-01-01
影响因子：
4.7
通讯作者：
Davis, ME
中科院分区：
文献类型：
--
作者：
Reineke, TM;Davis, ME
最近的聚阳离子结构-基因传递研究表明，聚阳离子分子结构的细微变化对DNA结合和缩合以及体外毒性和基因传递效率具有重大影响。在使用含碳水化合物的聚阳离子 (1) 的结构-性质研究的第 1 部分中，结果表明，随着脒电荷中心从聚阳离子结构内的碳水化合物单元进一步去除，毒性会增加。在聚阳离子主链内包含较大的碳水化合物种类也降低了毒性。在这里，研究了聚阳离子电荷中心类型对毒性和基因递送效率的影响。合成了一系列含有 N,N,N'N'-四甲基-1,6-己二胺、D-海藻糖和 β-环糊精的季铵聚阳离子，以阐明电荷中心类型（通过与第 1 部分中给出的数据进行比较）对基因递送的影响。在所有情况下，发现季铵类似物表现出较低的基因表达值和与其脒类似物相似的毒性。另外，转染。在氯喹存在下进行的实验表明，含季铵的聚阳离子而非脒类似物的基因表达增加。
Recent polycation structure-gene delivery studies reveal that subtle changes in the molecular structure of polycations have substantial influences on DNA-binding and condensation and on in vitro toxicity and gene delivery efficiency. In Part 1 of this structure-property study using carbohydrate-containing polycations (1), it is demonstrated that as the amidine charge center is removed further from the carbohydrate unit within the polycation structure, the toxicity increases. Inclusion of larger carbohydrate species within the polycation backbone also reduces the toxicity. Here, the effect that polycation charge center type has on toxicity and gene delivery efficiency is investigated. A series of quaternary ammonium polycations containing N,N,N'N'-tetramethyl-1,6-hexanediamine, D-trehalose, and beta-cyclodextrin are synthesized in order to elucidate the effects of charge center type (by comparison to the data given in Part 1) on gene delivery. In all cases, it is found that the quaternary ammonium analogues exhibit lower gene expression values and similar toxicities to their amidine analogues. Additionally, transfection. experiments conducted in the presence of chloroquine reveal increased gene expression from quaternary ammonium containing polycations and not from their amidine analogues.