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Rational Design of a Red Fluorescent Sensor for ALDH1A1 Displaying Enhanced Cellular Uptake and Reactivity.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2019-11-18 , DOI: 10.1021/acs.bioconjchem.9b00723 Thomas E Bearrood 1 , Guadalupe Aguirre-Figueroa 1 , Jefferson Chan 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2019-11-18 , DOI: 10.1021/acs.bioconjchem.9b00723 Thomas E Bearrood 1 , Guadalupe Aguirre-Figueroa 1 , Jefferson Chan 1
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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.
中文翻译：
用于ALDH1A1的红色荧光传感器的合理设计，该传感器显示增强的细胞摄取和反应性。
高醛脱氢酶1A1（ALDH1A1）活性已成为鉴定正常和癌症干细胞的可靠标记。为了促进干细胞的检测，分子成像和分选，最近开发了一种基于dye吨染料支架的绿色荧光探针。但是，绿色染料不适合多色成像，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。在此，我们报告了红色同类物red-AlDeSense的开发。通过化学调节，我们能够实现出色的同工型选择性和化学稳定性，良好的开启响应以及增强的细胞摄取和反应性。重要的，red-AlDeSense代表红色区域中使用d-PeT淬灭机制的少数几个打开传感器之一。通过使用红色的AlDeSense和绿色的抗CD44抗体，我们能够证明这两种干细胞标记物的染色在A549肺腺癌细胞中彼此独立。
更新日期：2019-11-19
中文翻译：
用于ALDH1A1的红色荧光传感器的合理设计，该传感器显示增强的细胞摄取和反应性。
高醛脱氢酶1A1（ALDH1A1）活性已成为鉴定正常和癌症干细胞的可靠标记。为了促进干细胞的检测，分子成像和分选，最近开发了一种基于dye吨染料支架的绿色荧光探针。但是，绿色染料不适合多色成像，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。在此，我们报告了红色同类物red-AlDeSense的开发。通过化学调节，我们能够实现出色的同工型选择性和化学稳定性，良好的开启响应以及增强的细胞摄取和反应性。重要的，red-AlDeSense代表红色区域中使用d-PeT淬灭机制的少数几个打开传感器之一。通过使用红色的AlDeSense和绿色的抗CD44抗体，我们能够证明这两种干细胞标记物的染色在A549肺腺癌细胞中彼此独立。
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