Kexin Wang, Ruoxi Wang, Zihui Yan, Yi Li, Yangchen Shi, Jing-Yuan Ge, Yang Bai, Zhongyan Chen, Lei Zhang
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引用次数: 0
摘要
通过无创动态成像追踪羧基酯酶(CES)对于诊断和治疗与 CES 相关的代谢性疾病具有重要意义。本文设计并合成了三种基于 BODIPY 的荧光探针,其吡啶单元通过乙酰氧基苄基季铵盐化,可在光诱导电子转移过程的基础上检测 CES。值得注意的是,在这些探针中,BDPN2-CES 在 10 分钟内对 CESs 的荧光增强了 182 倍。此外,BDPN2-CES 还成功实现了活细胞中内源性 CES 变化的实时成像。利用 BDPN2-CES,建立了一种可视化高通量筛选 CES 抑制剂的方法,最终从化学库中发现了一种高效抑制剂 WZU-13。这些发现表明,BDPN2-CES 可为诊断 CES 相关疾病提供一条新途径,而 WZU-13 则有望成为治疗 CES 过表达病理过程的候选药物。
Rational Design of a Highly Sensitive Carboxylesterase Probe and Its Application in High-Throughput Screening for Uncovering Carboxylesterase Inhibitors.
Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.
期刊介绍:
The Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.