Rational Design of a Red Fluorescent Sensor for ALDH1A1 Displaying Enhanced Cellular Uptake and Reactivity
Rational Design of a Red Fluorescent Sensor for ALDH1A1 Displaying Enhanced Cellular Uptake and Reactivity
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DOI：
10.1021/acs.bioconjchem.9b00723
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发表时间：
2020-02-01
影响因子：
4.7
通讯作者：
Chan, Jefferson
中科院分区：
文献类型：
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作者：
Bearrood, Thomas E.;Aguirre-Figueroa, Guadalupe;Chan, Jefferson
高醛脱氢酶1A1 （ALDH1A1）活性已成为识别正常和癌症干细胞的可靠标记。为了方便干细胞的检测、分子成像和分选，最近开发了一种基于杂蒽染料支架的绿色荧光探针。然而，绿色染料不太适合多色成像，因为大多数商业试剂也是绿色的。克服这一限制将使同时跟踪多个干细胞标记成为可能。在这里，我们报道了一种红色同系物——红色aldesense的发展。通过化学调整，我们能够获得优异的异构体选择性和化学稳定性，良好的转向反应，并增强细胞摄取和反应性。重要的是，red- aldesense代表了红色区域中使用d-PeT猝灭机制的少数开启传感器之一。通过使用红色aldesense和绿色抗cd44抗体，我们能够证明这两种干细胞标记物在A549肺腺癌细胞中的染色是相互独立的。
High aldehyde dehydrogenase 1A1 (ALDH1A1) activity has emerged as a reliable marker for the identification of both normal and cancer stem cells. To facilitate the detection, molecular imaging, and sorting of stem cells, a green fluorescent probe based on the xanthene dye scaffold was recently developed. However, green dyes are less amenable to multicolor imaging because most commercial reagents are also green. Overcoming this limitation will enable the simultaneous tracking of multiple stem cell markers. Herein, we report the development of a red congener, red-AlDeSense. Through chemical tuning we were able to achieve excellent isoform selectivity and chemostability, a good turn on response, and enhanced cellular uptake and reactivity. Importantly, red-AlDeSense represents one of only a few turn-on sensors in the red region that use the d-PeT quenching mechanism. By employing red-AlDeSense and a green anti-CD44 antibody, we were able to demonstrate staining of these two stem cell markers is independent of one another in A549 lung adenocarcinoma cells.