Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, School of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China.
Sci Adv. 2023 May 10;9(19):eadg2583. doi: 10.1126/sciadv.adg2583.
An obstacle to conducting diverse bioorthogonal reactions in living systems is the sensitivity of artificial metal catalysts. It has been reported that artificial metallocatalysts can be assembled in "cleaner" environments in cells for stabilized performance, which is powerful but is limited by the prerequisite of using specific cells. We report here a strategy to establish membrane-anchored catalysts with precise spatial control via liposome fusion-based transport (MAC-LiFT), loading bioorthogonal catalytic complexes onto either or both sides of the membrane leaflets. We show that the inner face of the cytoplasmic membrane serves as a reliable shelter for metal centers, protecting the complexes from deactivation thus substantially lowering the amount of catalyst needed for effective intracellular catalysis. This MAC-LiFT approach makes it possible to establish catalyst-protective systems with exclusively exogenous agents in a wide array of mammalian cells, allowing convenient and wider use of diverse bioorthogonal reactions in live cellular systems.
在活细胞系统中进行多种生物正交反应的一个障碍是人工金属催化剂的敏感性。据报道，人工金属催化剂可以在细胞内“更清洁”的环境中组装，以获得更稳定的性能，这是一种强大的方法，但受到使用特定细胞的前提条件的限制。我们在这里报告了一种通过基于脂质体融合的转运（MAC-LiFT）建立具有精确空间控制的膜锚定催化剂的策略，将生物正交催化配合物加载到膜小叶的一侧或两侧。我们表明，细胞质膜的内表面可作为金属中心的可靠庇护所，保护配合物免于失活，从而大大降低了有效进行细胞内催化所需的催化剂用量。这种 MAC-LiFT 方法使得有可能在广泛的哺乳动物细胞中建立仅用外源试剂的催化剂保护系统，从而方便且更广泛地在活细胞系统中使用多种生物正交反应。
