Enzyme-instructed self-assembly of taxol promotes axonal branching
Enzyme-instructed self-assembly of taxol promotes axonal branching
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酶指导的紫杉醇自组装促进轴突分支
DOI：
10.1039/c5nr04563k
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发表时间：
2015
期刊：
影响因子：
6.7
通讯作者：
Liang Gaolin
中科院分区：
文献类型：
--
作者：
Mei Bin;Miao Qingqing;Tang Anming;Liang Gaolin
轴突分支是脊椎动物神经元信号传导的重要组成部分。紫杉醇对轴突分支有双相作用（高浓度抑制轴突生长，低浓度恢复轴突生长）。据我们所知，低浓度紫杉醇促进轴突分支尚未见报道。在此，我们合理设计了一种紫杉醇衍生物fmoc - ph - ph - lys (taxol)-Tyr(H2PO4)-OH(1)，该衍生物可以通过碱性磷酸酶（ALP）催化自组装形成紫杉醇纳米纤维。我们发现，在10 μM时，1具有与紫杉醇相似的微管（MT）凝聚作用，但对细胞的慢性毒性比紫杉醇更大。在低浓度10 nM下，1不仅像紫杉醇一样促进了神经突的伸长，而且还促进了轴突的分支，这是紫杉醇所没有的。我们认为沿mt的自组装阻止了它们的横向接触，从而促进了轴突分支。我们的紫杉醇衍生物的酶指示自组装（EISA）策略为科学家研究神经元的形态及其行为提供了一种新的工具。
Axonal branching is important for vertebrate neuron signaling. Taxol has a biphasic effect on axonal branching (i.e., high concentration inhibits axonal growth but low concentration restores it). To the best of our knowledge, low concentration of taxol to promote axonal branching has not been reported yet. Herein, we rationally designed a taxol derivative Fmoc-Phe-Phe-Lys(taxol)-Tyr(H2PO4)-OH (1) which could be subjected to alkaline phosphatase (ALP)-catalyzed self-assembly to form taxol nanofibers. We found that, at 10 μM, 1 has a microtubule (MT) condensation effect similar to that of taxol on mammalian cells but with more chronic toxicity than taxol on the cells. At a low concentration of 10 nM, 1 not only promoted neurite elongation as taxol did but also promoted axonal branching which was not achieved by using taxol. We propose that self-assembly of 1 along the MTs prohibited their lateral contacts and thus promoted axonal branching. Our strategy of enzyme-instructed self-assembly (EISA) of a taxol derivative provides a new tool for scientists to study the morphology of neurons, as well as their behaviours.