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Bio-orthogonal Toolbox for Monitoring Nitric Oxide in Targeted Organelles of Live Cells and Zebrafishes
Analytical Chemistry ( IF 6.7 ) Pub Date : 2022-11-03 , DOI: 10.1021/acs.analchem.2c02768
Lin Zhou 1 , Chuanhao Liu 2 , Ying Zheng 1 , Zhenlong Huang 1 , Xinfu Zhang 1 , Yi Xiao 1
Affiliation  

Nitric oxide (NO), playing crucial roles as a cellular messenger and as a toxic ROS, is highly related to the physiological and pathological states of living systems. The very wide but very uneven distribution of this radical gas in the inhomogeneous biological microenvironment imposes big challenges for specifically detecting its local level in certain subcellular areas, which calls for a long list of NO probes for each target. In order to simplify the syntheses and designs of these probes, herein it is proposed to construct a versatile NO-sensing toolbox based on a bio-orthogonal concept, i.e., inverse electron demand Diels–Alder click reaction between tetrazine and strained alkyne BCN. On the one hand, rhodamine-o-phenylenediamine as the NO-responsive scaffold is coupled with a tetrazine unit to generate a general probe TMR-Tz-NO, which, to our knowledge, is the first case of the tetrazine-coupled analyte-responsive probe. On the other hand, the BCN moiety is connected to different targeting groups, such as TPP, morpholine, and Ac4ManN, targeting to mitochondria, lysosomes, and membranes, respectively. It works well to use TMR-Tz-NO to match with any targetable BCN counterpart in this toolbox to achieve the imaging of NO in the corresponding subcellular area. For example, through metabolism, Ac4ManN-BCN is effectively taken and grows on the cell membranes. The bio-orthogonal reaction between TMR-Tz-NO and Ac4ManN-BCN makes the NO probe anchored to the membrane surface permanently. The zebrafish experiment revealed that this bio-orthogonal pair can track and image the NO produced during inflammation in vivo.

中文翻译:

用于监测活细胞和斑马鱼靶向细胞器中一氧化氮的生物正交工具箱

一氧化氮 (NO) 作为细胞信使和有毒 ROS 发挥着至关重要的作用,与生命系统的生理和病理状态高度相关。这种自由基气体在不均匀的生物微环境中非常广泛但非常不均匀的分布给在某些亚细胞区域特异性检测其局部水平带来了巨大挑战,这需要针对每个目标的一长串 NO 探针。为了简化这些探针的合成和设计,本文建议构建一个基于生物正交概念的多功能 NO 传感工具箱,即四嗪和应变炔烃 BCN 之间的逆电子需求 Diels-Alder 点击反应。一方面,罗丹明-o-苯二胺作为 NO 响应支架与四嗪单元偶联生成通用探针 TMR-Tz-NO,据我们所知,这是四嗪偶联分析物响应探针的第一个案例。另一方面,BCN 部分连接到不同的靶向基团,例如 TPP、吗啉和 Ac 4 ManN,分别靶向线粒体、溶酶体和膜。使用 TMR-Tz-NO 与此工具箱中任何可靶向 BCN 对应物匹配,以实现相应亚细胞区域中 NO 的成像,效果很好。例如,通过新陈代谢,Ac 4 ManN-BCN 被有效地吸收并在细胞膜上生长。TMR-Tz-NO与Ac 4的生物正交反应ManN-BCN 使 NO 探针永久固定在膜表面。斑马鱼实验表明,这种生物正交对可以跟踪和成像体内炎症过程中产生的 NO。
更新日期:2022-11-03
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