An Optimized Two-Photon Fluorescent Probe for Biological Sensing and Imaging of Catechol-O-Methyltransferase
An Optimized Two-Photon Fluorescent Probe for Biological Sensing and Imaging of Catechol-O-Methyltransferase
复制标题
用于儿茶酚-O-甲基转移酶生物传感和成像的优化双光子荧光探针
DOI：
10.1002/chem.201701384
复制
发表时间：
2017-08-10
影响因子：
4.3
通讯作者：
Yang, Ling
中科院分区：
文献类型：
--
作者：
Wang, Ping;Xia, Yang-Liu;Yang, Ling
开发了一种实用的双光子荧光探针，用于高灵敏度、高选择性地检测复杂生物样品中儿茶酚 - O - 甲基转移酶（COMT）的活性。为此，设计并合成了一系列3 - 取代的7,8 - 二羟基香豆素。其中，3 - BTD在COMT催化的8 - O - 甲基化反应后，展现出选择性、灵敏度、反应性和荧光响应的最佳组合。新开发的双光子荧光探针3 - BTD可用于测定复杂生物样品中COMT的活性，以及对活细胞和组织切片中的内源性COMT进行生物成像，具有良好的细胞通透性、低细胞毒性和高成像分辨率。所有这些研究结果表明，3 - BTD在开发以COMT为靶点的治疗性分子，以及探索COMT相关的生物过程及其在生命系统中的生物学功能方面极具潜力。此外，该策略也为开发针对其他结合酶的荧光探针提供了新思路。
A practical two-photon fluorescent probe was developed for highly sensitive and selective sensing of the activities of catechol-O-methyltransferase (COMT) in complex biological samples. To this end, a series of 3-substituted 7,8-dihydroxycoumarins were designed and synthesized. Among them, 3-BTD displayed the best combination of selectivity, sensitivity, reactivity, and fluorescence response following COMT-catalyzed 8-O-methylation. The newly developed two-photon fluorescent probe 3-BTD can be used for determining the activities of COMT in complex biological samples and bio-imaging of endogenous COMT in living cells and tissue slices with good cell permeability, low cytotoxicity, and high imaging resolution. All these findings suggest that 3-BTD holds great promise for developing therapeutic molecules that target COMT, as well as for exploring COMT-associated biological processes and its biological functions in living systems. Furthermore, the strategy also sheds new light on the development of fluorescent probes for other conjugative enzymes.