Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian-Cancer-Specific γ-Glutamyltranspeptidase
Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian-Cancer-Specific γ-Glutamyltranspeptidase
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用于卵巢癌特异性 γ-谷氨酰转肽酶快速成像的荧光原位靶向探针
DOI：
10.1002/anie.201502899
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发表时间：
2015-06-15
影响因子：
16.6
通讯作者：
Fan, Chunhai
中科院分区：
文献类型：
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作者：
Wang, Feiyi;Zhu, Ying;Fan, Chunhai
γ -谷氨酰转肽酶（gamma-Glutamyltranspeptidase， GGT）是一种选择性催化肿瘤细胞质膜上过表达谷氨酸裂解的肿瘤生物标志物。在这里，我们开发了两种新的荧光原位靶向（FIST）探针，专门针对肿瘤细胞中的GGT，它们包括1)GGT特异性底物单位（GSH）和2)用于荧光信号传导的硼-二吡罗甲烷（BODIPY）片段。在GGT存在下，硫取代的BODIPY转化为氨基取代的BODIPY，导致显著的荧光变化。利用这种酶触发的光物理特性，我们利用这些拳头探针监测活细胞中的GGT活性，发现卵巢癌细胞与正常细胞之间存在显著的分化。这些探针代表了两种第一代化学剂量计，具有酶介导的快速，不可逆的芳烃在硫原子和氮原子之间转移，并伴有光物理性质的切换。
gamma-Glutamyltranspeptidase (GGT) is a tumor biomarker that selectively catalyzes the cleavage of glutamate overexpressed on the plasma membrane of tumor cells. Here, we developed two novel fluorescent in situ targeting (FIST) probes that specifically target GGT in tumor cells, which comprise 1) a GGT-specific substrate unit (GSH), and 2) a boron-dipyrromethene (BODIPY) moiety for fluorescent signalling. In the presence of GGT, sulfur-substituted BODIPY was converted to amino-substituted BODIPY, resulting in dramatic fluorescence variations. By exploiting this enzyme-triggered photophysical property, we employed these FIST probes to monitor the GGT activity in living cells, which showed remarkable differentiation between ovarian cancer cells and normal cells. These probes represent two first-generation chemodosimeters featuring enzyme-mediated rapid, irreversible aromatic hydrocarbon transfer between the sulfur and nitrogen atoms accompanied by switching of photophysical properties.