Völker Timo, Meggers Eric
Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043, Marburg, Germany.
Chembiochem. 2017 Jun 19;18(12):1083-1086. doi: 10.1002/cbic.201700168. Epub 2017 May 16.
Chemical (as opposed to light-induced) activation of caged molecules is a rapidly advancing approach to trigger biological processes. We previously introduced the ruthenium-catalyzed release of allyloxycarbonyl (alloc)-protected amines in human cells. A restriction of this and all other methods is the limited lifetime of the catalyst, thus hampering meaningful applications. In this study, we addressed this problem with the development of a new generation of ruthenium complexes for the uncaging of alloc-protected amines with superior catalytic activity. Under biologically relevant conditions, we achieved a turnover number >300, a reaction rate of 580 m s , and we observed high activity in blood serum. Furthermore, alloc-protected doxorubicin, as an anticancer prodrug, could be activated in human cell culture and induced apoptosis with a single low dose (1 μm) of the new catalyst.
笼形分子的化学（相对于光诱导）活化是一种迅速发展的触发生物过程的方法。我们之前在人类细胞中引入了钌催化的烯丙氧羰基（alloc）保护胺的释放。这种方法以及所有其他方法的一个限制是催化剂的寿命有限，从而阻碍了有意义的应用。在本研究中，我们通过开发新一代用于释放alloc保护胺的具有卓越催化活性的钌配合物来解决这个问题。在生物学相关条件下，我们实现了周转数>300，反应速率为580 m s，并且在血清中观察到高活性。此外，alloc保护的阿霉素作为一种抗癌前药，可以在人类细胞培养中被激活，并且用单一低剂量（1μm）的新催化剂诱导细胞凋亡。
