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Controlled Supramolecular Assembly inside Living Cells by Sequential Multi-staged Chemical Reactions
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2020-08-19 , DOI: 10.1021/jacs.0c05261
Michaela Pieszka 1, 2 , Shen Han 1 , Christiane Volkmann 1 , Robert Graf 1 , Ingo Lieberwirth 1 , Katharina Landfester 1 , David Y W Ng 1 , Tanja Weil 1, 2
Affiliation  

Synthetic assembly within living cells represents an innovative way to explore purely chemical tools that can direct and control cellular behavior. We use a simple and modular platform that is broadly accessible and yet incorporates highly intricate molecular recognition, immolative, and rearrangement chemistry. Short bimodular peptide sequences undergo a programmed sequence of events that can be tailored within the living intracellular environment. Each sequential stage of the pathways beginning with the cellular uptake, intracellular transport, and localization imposes distinct structural changes that result in the assembly of fibrillar architectures inside cells. The observation of apoptosis, which is characterized by the binding of Annexin V, demonstrates that programmed cell death can be promoted by the peptide assembly. Higher complexity of the assemblies was also achieved by coassembly of two different sequences, resulting in intrinsically fluorescent architectures. As such, we demonstrate that the in situ construction of architectures within cells will broaden the community’s perspective toward how structure formation can impact a living system.

中文翻译:

通过顺序多阶段化学反应控制活细胞内的超分子组装

活细胞内的合成组装代表了一种探索可以指导和控制细胞行为的纯化学工具的创新方式。我们使用一个简单和模块化的平台,该平台可广泛使用,但结合了高度复杂的分子识别、分解和重排化学。短的双模块肽序列经过程序化的事件序列,可以在活的细胞内环境中进行调整。从细胞摄取、细胞内转运和定位开始的通路的每个连续阶段都会施加不同的结构变化,导致细胞内纤维结构的组装。观察到以膜联蛋白 V 结合为特征的细胞凋亡,表明肽组装可以促进程序性细胞死亡。两个不同序列的共组装也实现了组装的更高复杂性,从而产生了固有的荧光结构。因此,我们证明细胞内建筑的原位构建将拓宽社区对结构形成如何影响生命系统的看法。
更新日期:2020-08-19
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