Translocation of an Intracellular Protein via Peptide-Directed Ligation.

Translocation of an Intracellular Protein via Peptide-Directed Ligation.
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通过肽定向连接实现细胞内蛋白质的易位

DOI:
10.1021/acschembio.6b01013
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发表时间:
2017
影响因子:
4
通讯作者:
TN Grossmann
TN Grossmann
中科院分区:
生物学2区
文献类型:
--
作者:
C Stiller;DM Krüger;N Brauckhoff;M Schmidt;P Janning;H Salamon;TN Grossmann

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配体导向反应允许在非常低的反应物浓度下进行化学转化,因此可以提供用于蛋白质翻译后修饰的有效方法。这些邻近诱导反应的发展受到适当配体数量和缺乏设计原则的阻碍。针对这些限制,我们报告了一个接近诱导的标记系统,适用于中等亲和力的肽配体。设计过程是结构指导和分子动力学模拟的支持。我们表明,选择性的蛋白质标记可以在活细胞内进行,使蛋白质的亚细胞易位通过配体定向化学第一次。
Ligand-directed reactions allow chemical transformations at very low reactant concentrations and can thus provide access to efficient approaches for the post-translational modification of proteins. The development of these proximity-induced reactions is hampered by the number of appropriate ligands and the lack of design principles. Addressing these limitations, we report a proximity-induced labeling system which applies a moderate affinity peptide ligand. The design process was structure-guided and supported by molecular dynamics simulations. We show that selective protein labeling can be performed inside living cells enabling the subcellular translocation of a protein via ligand-directed chemistry for the first time.
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