Regulating the Rate of Molecular Self-Assembly for Targeting Cancer Cells.
Regulating the Rate of Molecular Self-Assembly for Targeting Cancer Cells.
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DOI：
10.1002/anie.201600753
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发表时间：
2016-05-04
期刊：
影响因子：
--
通讯作者：
Xu B
中科院分区：
文献类型：
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作者：
Zhou J;Du X;Xu B
除了紧密和特异的配体-受体相互作用外，分子组装体形成的速率调节是细胞的基本特征之一。但后者很少受到开发抗癌疗法的探索。在这里，我们表明，一个简单的分子设计的磷酸酶的底物-剪裁肽底物上的磷酸盐的数量-是能够调节的酶反应产物的分子自组装的速率。这种速率调节允许选择性抑制骨肉瘤细胞而不是肝细胞，这有望靶向特定器官中的癌细胞。此外，我们的结果表明，在基于细胞的测定中直接测量自组装的速率提供了自组装的细胞靶向能力的精确评估。这项工作，作为第一份报告，建立了多步骤过程的速率调节，以选择性地抑制细胞，说明了一个从根本上控制细胞命运的新方法。调整肽底物上磷酸盐的数量能够调节酶反应产物的自组装速率。这种速率调节允许选择性抑制骨肉瘤细胞而不是肝细胞，这有望靶向特定器官中的癌细胞。作为第一个使用多步过程的速率调节来选择性抑制细胞的报告，这项工作说明了一种从根本上控制细胞命运的新方法。
Besides tight and specific ligand-receptor interactions, the rate regulation of the formation of molecular assemblies is one of fundamental features of cells. But the latter receives little exploration for developing anticancer therapeutics. Here we show that a simple molecular design of the substrates of phosphatases—tailoring the number of phosphates on peptidic substrates—is able to regulate the rate of molecular self-assembly of the enzyme reaction product. Such a rate regulation allows selective inhibition of osteosarcoma cells over hepatocytes, which promises to target cancer cells in a specific organ. Moreover, our result reveals that the direct measurement of the rate of the self-assembly in a cell-based assay provides precise assessment of the cell targeting capability of self-assembly. This work, as the first report establishing rate regulation of a multiple-step process to inhibit cells selectively, illustrates a fundamentally new approach for controlling the fate of cells. Tailoring the number of phosphates on peptidic substrate is able to regulate the rate of self-assembly of the enzyme reaction product. Such a rate regulation allows selective inhibition of osteosarcoma cells over hepatocytes, which promises to target cancer cells in a specific organ. As the first report of using rate regulation of a multiple-step process to inhibit cells selectively, this work illustrates a fundamentally new approach to control the fate of cells.