Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia
Efficient, non-toxic anion transport by synthetic carriers in cells and epithelia
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DOI：
10.1038/nchem.2384
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发表时间：
2016-01-01
期刊：
影响因子：
21.8
通讯作者：
Davis, Anthony P.
中科院分区：
文献类型：
--
作者：
Li, Hongyu;Valkenier, Hennie;Davis, Anthony P.
跨膜阴离子转运蛋白（阴离子载体）具有新的生物活性模式的潜力，包括治疗应用。特别是，它们可能在囊性纤维化等疾病中取代有缺陷的阴离子通道的活性。然而，关于阴离子载体的生物效应的数据很少，并且仍然不确定这些分子是否从根本上有毒。在这里，我们报告了一个广泛的系列强大的阴离子载体的生物学研究。在单细胞中通过监测阴离子转运在真实的时间通过荧光发射从卤素敏感的黄色荧光蛋白测定15阴离子载体。双-（对硝基苯基）脲十二烷酮显示出特别有前景的活性，包括可递送性、效力和持久性。电生理测试显示在上皮细胞中的强效应，接近于天然阴离子通道的效应。毒性试验在三个细胞系中产生阴性结果，表明促进阴离子转运可能对细胞无害。因此，我们得出结论，合成阴离子载体是现实的候选人，进一步调查作为治疗囊性纤维化。
Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl) ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.