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工程核酸和合成辅因子作为全分子传感器,用于探测细胞膜微环境中的信号分子。

Engineering of Nucleic Acids and Synthetic Cofactors as Holo Sensors for Probing Signaling Molecules in the Cellular Membrane Microenvironment.

机构信息

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha, 410082, P. R. China.

Pharmaceutical Engineering & Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China.

出版信息

Angew Chem Int Ed Engl. 2019 May 13;58(20):6590-6594. doi: 10.1002/anie.201901320. Epub 2019 Mar 20.

DOI:10.1002/anie.201901320
PMID:30843301
Abstract

The comprehensive understanding of the mechanisms underlying the interaction of cells with their membrane microenvironment is of great value for fundamental biological research; however, tracking biomolecules on cell surfaces with high temporal and spatial resolution remains a challenge. Herein, a modular strategy is presented for the construction of cell surface DNA-based sensors by engineering DNA motifs and synthetic cofactors. In this strategy, a stimuli-reactive organic molecule is employed as the cofactor for the DNA motif, and the self-assembly of them forms a FRET-based holo DNA-based sensor. With the use of the DNA-based sensors, the versatility of this modular strategy has been demonstrated in the ratiometric imaging of the cellular extrusion process of endogenous signaling molecules, including sulfur dioxide derivatives and nitric oxide.

摘要

深入理解细胞与其膜微环境相互作用的机制对于基础生物学研究具有重要价值;然而,以高时间和空间分辨率跟踪细胞表面上的生物分子仍然是一个挑战。在此,通过工程化 DNA 基元和合成辅因子,提出了一种构建基于 DNA 的细胞表面传感器的模块化策略。在此策略中,将响应刺激的有机分子用作 DNA 基元的辅因子,它们的自组装形成基于 FRET 的整体 DNA 基传感器。使用基于 DNA 的传感器,该模块化策略的多功能性已在细胞内源性信号分子(包括二氧化硫衍生物和一氧化氮)的细胞挤出过程的比率成像中得到了证明。

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