para-Nitroblebbistatin, the Non-Cytotoxic and Photostable Myosin II Inhibitor
para-Nitroblebbistatin, the Non-Cytotoxic and Photostable Myosin II Inhibitor
复制标题
DOI：
10.1002/anie.201403540
复制
发表时间：
2014-07-28
影响因子：
16.6
通讯作者：
Malnasi-Csizmadia, Andras
中科院分区：
文献类型：
--
作者：
Kepiro, Miklos;Varkuti, Boglarka H.;Malnasi-Csizmadia, Andras
Blebbistatin是最具特征的肌球蛋白II抑制剂，常用于研究各种肌球蛋白II亚型的生物学作用。尽管其受欢迎，但其蓝光敏感性极大地阻碍了blebbistatin的使用，导致分子的光毒性和光转化。此外，即使在没有照射的情况下，blebbistatin也具有严重的细胞毒性副作用，这可能容易导致对实验结果的误解，因为细胞毒性衍生的表型可能归因于对肌球蛋白II功能的抑制。在这里，我们报告的合成以及在体外和体内表征的光稳定性，C15硝基衍生物的blebbistatin与不受影响的肌球蛋白II抑制性能。重要的是，对硝基blebbistatin既没有光毒性也没有细胞毒性，如细胞和动物试验所示;因此，它可以在体外和体内作为blebbistatin的无限制和完全替代品。
Blebbistatin, the best characterized myosin II-inhibitor, is commonly used to study the biological roles of various myosin II isoforms. Despite its popularity, the use of blebbistatin is greatly hindered by its blue-light sensitivity, resulting in phototoxicity and photoconversion of the molecule. Additionally, blebbistatin has serious cytotoxic side effects even in the absence of irradiation, which may easily lead to the misinterpretation of experimental results since the cytotoxicity-derived phenotype could be attributed to the inhibition of the myosin II function. Here we report the synthesis as well as the in vitro and in vivo characterization of a photostable, C15 nitro derivative of blebbistatin with unaffected myosin II inhibitory properties. Importantly, para-nitroblebbistatin is neither phototoxic nor cytotoxic, as shown by cellular and animal tests; therefore it can serve as an unrestricted and complete replacement of blebbistatin both in vitro and in vivo.