Chemical Activation in Blood Serum and Human Cell Culture: Improved Ruthenium Complex for Catalytic Uncaging of Alloc‐Protected Amines |
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Authors: | Timo Völker Prof?Dr Eric Meggers |
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Affiliation: | Philipps-Universit?t Marburg, Marburg, Germany |
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Abstract: | 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 ?1 s?1, 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. |
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Keywords: | bioorthogonal chemistry cage compounds catalysis drug delivery ruthenium uncaging |
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