荧光
荧光团
流出
化学
香豆素
流式细胞术
微管
生物物理学
细胞内
羧酸
组合化学
生物化学
生物
细胞生物学
有机化学
分子生物学
物理
量子力学
作者
Digamber Rane,Anver Basha Shaik,Szu Lee,Xiaojun Hu,Blake R. Peterson
标识
DOI:10.1021/acsmedchemlett.4c00085
摘要
To facilitate studies of engagement of protein targets by small molecules in living cells, we synthesized fluorinated derivatives of the fluorophore 7-hydroxycoumarin-3-carboxylic acid (7OHCCA). Compared to the related difluorinated coumarin Pacific Blue (PB), amide derivatives of 6-fluoro-7-hydroxycoumarin-3-carboxylic acid (6FC) exhibited substantially brighter fluorescence. When linked to the anticancer drug paclitaxel (Taxol) via gamma-aminobutyric acid (GABA), the acidity of the phenol of these coumarins profoundly affected cellular efflux and binding to microtubules in living cells. In contrast to the known fluorescent taxoid PB-GABA-Taxol, the less acidic 6FC-GABA-Taxol was more cell-permeable due to a lower susceptibility to active efflux. In living cells, this facilitated the imaging of microtubules by confocal microscopy and enabled quantification of binding to microtubules by flow cytometry without added efflux inhibitors. The photophysical, chemical, and biological properties of 6FC derivatives make these compounds particularly attractive for the construction of fluorescent molecular probes suitable for quantitative analysis of intracellular small molecule–protein interactions.
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