新型四苯乙烯衍生物的设计合成及其在羧酸酯酶活性分析中的应用

doi:10.6023/A16080415

化学学报 ›› 2016, Vol. 74 ›› Issue (11): 871-876.DOI: 10.6023/A16080415 上一篇下一篇

研究论文

新型四苯乙烯衍生物的设计合成及其在羧酸酯酶活性分析中的应用

杨阳^a,b, 黄嫣嫣^a,b, 张关心^a, 赵睿^a,b, 张德清^a,b

a 中国科学院化学研究所有机固体院重点实验室活体分析院重点实验室北京 100190;
b 中国科学院大学北京 100049

投稿日期:2016-08-15 发布日期:2016-10-10
通讯作者: 张关心, 张德清 E-mail:dqzhang@iccas.ac.cn
基金资助:
项目受科技部国家重点基础研究发展计划（Nos.2013CB733700，2013CB834700）和北京市自然科学基金（No.2162048）资助.

A New Fluorometric Turn-on Assay for Carboxylesterase and Inhibitor Screening Based on Aggregation Induced Emission Behavior of Tetraphenylethylene Molecules

Yang Yang^a,b, Huang Yanyan^a,b, Zhang Guanxin^a, Zhao Rui^a,b, Zhang Deqing^a,b

a CAS Key Laboratories of Organic Solids and Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190;
b University of Chinese Academy of Sciences, Beijing 100049

Received:2016-08-15 Published:2016-10-10
Supported by:
Project supported by the 973 Program (Nos. 2013CB733700, 2013CB834700) and Beijing Natural Science Foundation (No. 2162048).

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1. 新型四苯乙烯衍生物的设计合成及其在羧酸酯酶活性分析中的应用.PDF(291KB)

摘要/Abstract

设计合成了一个含有p-乙酰氧基苄基单元的四苯乙烯吡啶盐衍生物，利用羧酸酯酶选择性地切除乙酰基以及所致的连锁反应将其从水溶性吡啶盐结构转为中性吡啶结构，使其聚集，实现荧光“点亮”，从而发展了新型的羧酸酯酶活性分析和抑制剂筛选的荧光探针.

关键词: 聚集诱导发光, 四苯乙烯, 荧光传感器, 羧酸酯酶

It is known that carboxylesterase (CaE) are a group of isoenzymes commonly distributed in mammalian organs, and they can catalyze the hydrolysis of carboxyl ester. As a result, they play an important role in detoxification of narcotics or chemical toxin clearance. Moreover, they serve as important drug candidates for protein-based therapeutics or drug targets for chemotherapeutic prodrug activation. It is reported recently that human plasma carboxylesterase can be a novel biomarker candidate for hepatocellular carcinoma. Therefore, establishing a reliable fluorescent system for detecting carboxylesterase is of great importance in terms of biochemical studies as well as clinical applications. Herein, we report a new fluorometric turn-on assay for carboxylesterase activity and inhibitor screening with compound 1 by utilizing the aggregation-induced emission (AIE) feature of tetraphenylethylene (TPE) molecules. The sensing mechanism is illustrated in Figure 1 and explains as follows:(i) the pyridinium moiety may render compound 1 water-soluble. As a result it is anticipated that compound 1 is weakly emissive in aqueous solutions according to previous studies; (ii) the incubation of carboxylesterase with compound 1 can result in cleaving the carboxylic ester bond, followed by hydrolysis and 1,6-elimination of p-quinonemethide to yield the p-pyridine substituted TPE (TPE-Py). TPE-Py is not soluble in aqueous solutions, thus aggregation will occur and turn on the fluorescence of TPE moiety based on the AIE feature of TPE compounds. In this way, compound 1 can be employed for the fluorescence turn-on assay for carboxylesterase activity. The results reveal that the buffer solution of compound 1 emitted very weakly. However, the green fluorescence emission was switched on after addition of carboxylesterase. Carboxylesterase at concentrations as low as 5.67×10^-5 U/mL can be assayed with compound 1. Further results clearly indicate that compound 1 can be utilized not only for carboxylesterase activity assay but also for the corresponding inhibitor screening. More importantly, this probe can be applied for detection of carboxylesterases in living cells.

Key words: aggregation induced emission, tetraphenylethylene, fluorescence sensor, carboxylesterase

引用此文

杨阳, 黄嫣嫣, 张关心, 赵睿, 张德清. 新型四苯乙烯衍生物的设计合成及其在羧酸酯酶活性分析中的应用[J]. 化学学报, 2016, 74(11): 871-876.

Yang Yang, Huang Yanyan, Zhang Guanxin, Zhao Rui, Zhang Deqing. A New Fluorometric Turn-on Assay for Carboxylesterase and Inhibitor Screening Based on Aggregation Induced Emission Behavior of Tetraphenylethylene Molecules[J]. Acta Chim. Sinica, 2016, 74(11): 871-876.

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新型四苯乙烯衍生物的设计合成及其在羧酸酯酶活性分析中的应用

A New Fluorometric Turn-on Assay for Carboxylesterase and Inhibitor Screening Based on Aggregation Induced Emission Behavior of Tetraphenylethylene Molecules

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