Steric Control in Activator-Induced Nucleophilic Quencher Detachment-Based Probes: High-Contrast Imaging of Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells
Steric Control in Activator-Induced Nucleophilic Quencher Detachment-Based Probes: High-Contrast Imaging of Aldehyde Dehydrogenase 1A1 in Cancer Stem Cells
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DOI：
10.1002/cplu.202200319
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发表时间：
2022-11-01
期刊：
影响因子：
3.4
通讯作者：
Ohe，Kouichi
中科院分区：
文献类型：
--
作者：
Oe，Masahiro;Suzuki，Kanae;Ohe，Kouichi
开启的荧光探针可以以高对比度可视化酶的活性。我们建立了一种新的启动机制，即激活剂诱导的亲核猝灭剂脱离(AiQd)，并开发了基于AiQd的启动荧光探针用于酶的检测。在这里，我们证明了精确的空间位阻控制有效地在酶转化之前猝灭了基于AiQd的开启探针的荧光。理论计算恰当地预测了荧光猝灭的闭环型探针的比例。βC5S-A在荧光猝灭的亲核巯基的β位置具有空间要求的甲基，显示出低背景信号。βC5S-A对乙醛脱氢酶1A1(ALDH1A1)有高选择性的反应，从而实现了癌症干细胞的高对比度实时成像(信噪比10)。氨基酸和生物硫醇，如半胱氨酸和谷胱甘肽对βC5S-A的ALDH1A1响应性没有显著影响。
Turn‐on fluorescence probes can visualize the enzyme activity with high contrast. We have established a new turn‐on mechanism, activator‐induced nucleophilic quencher detachment (AiQd), and developed AiQd‐based turn‐on fluorescence probes for the detection of enzymes. Herein, we demonstrate that the precise steric control efficiently quenches the fluorescence of AiQd‐based turn‐on probes before the enzymatic transformation. Theoretical calculation appropriately predicted the ratio of the fluorescence‐quenched closed‐ring form of probes.βC5S‐A, which has a sterically demanding methyl group at the β‐position of a fluorescence‐quenching nucleophilic mercapto group, showed a low background signal.βC5S‐Aresponded to aldehyde dehydrogenase 1A1 (ALDH1A1) with high selectivity, thereby enabling high‐contrast live imaging of cancer stem cells (signal‐to‐noise ratio >10). The ALDH1A1‐responsiveness ofβC5S‐Awas not significantly affected by amino acids and biological thiols, such as cysteine and glutathione.