Simple isomeric pyridine-based fluorescence-off probes for in vitro monitoring γ-glutamyltranspeptidase activity: Design, synthesis and application

IF 4.1 3区工程技术 Q2 CHEMISTRY, APPLIED Dyes and Pigments Pub Date : 2024-05-31 DOI:10.1016/j.dyepig.2024.112252

Chen He , Hua Wang , Li Fu , Qi Wang , Yingfang Zhong , Mimi Zeng , Xiaofeng Lin , Junyun Huang , Jun Xie , Qitong Huang , Min Yang

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Abstract

γ-Glutamyltranspeptidase (GGT) is a cell surface-associated enzyme, which has been proven to be closely related to many diseases. Thus, development of simple and effective GGT-activatable fluorescent probes for early diagnosis of diseases is of great significance. Herein, a series of simple isomeric pyridine-based GGT-activatable fluorescent probes has been successfully designed and synthesized. The preliminary experimental results indicate that Py-GGT-1 has a significant fluorescence response to GGT via a rare fluorescence-off approach. Further fluorescence response experiments, such as the time-/dose-dependent fluorescence change and the selectivity/specificity estimation, reveal that Py-GGT-1 has an excellent ability to monitor endogenous GGT activity. Mechanism studies through HRMS analysis, DFT calculations and molecular docking have theoretically verified the catalytic process between Py-GGT-1 and GGT. To develop its practical application, live-cell imaging and serum-sample analysis were carried out, demonstrating that Py-GGT-1 coud effectively track GGT within cells and organisms. Based its high selectivity and reasonable sensitivity, we expect that the probe will be applied in clinical diagnosis of GGT-related diseases in the future.

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用于体外监测γ-谷氨酰转肽酶活性的简单异构吡啶荧光探针：设计、合成和应用

γ-谷氨酰转肽酶（GGT）是一种细胞表面相关酶，已被证实与多种疾病密切相关。因此，开发简单有效的可激活 GGT 的荧光探针用于疾病的早期诊断具有重要意义。本文成功设计并合成了一系列基于吡啶的简单异构体 GGT 可激活荧光探针。初步实验结果表明，Py-GGT-1 通过一种罕见的荧光关闭方法对 GGT 具有显著的荧光响应。进一步的荧光响应实验，如时间/剂量依赖性荧光变化和选择性/特异性估计，表明 Py-GGT-1 具有良好的监测内源性 GGT 活性的能力。通过 HRMS 分析、DFT 计算和分子对接进行的机理研究从理论上验证了 Py-GGT-1 与 GGT 之间的催化过程。为了开发其实际应用，研究人员进行了活细胞成像和血清样本分析，证明 Py-GGT-1 可以有效追踪细胞和生物体内的 GGT。基于该探针的高选择性和合理的灵敏度，我们期待它将来能应用于 GGT 相关疾病的临床诊断。

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来源期刊

Dyes and Pigments 工程技术-材料科学：纺织

CiteScore

8.20

自引率

13.30%

发文量

933

审稿时长

33 days

期刊介绍： Dyes and Pigments covers the scientific and technical aspects of the chemistry and physics of dyes, pigments and their intermediates. Emphasis is placed on the properties of the colouring matters themselves rather than on their applications or the system in which they may be applied. Thus the journal accepts research and review papers on the synthesis of dyes, pigments and intermediates, their physical or chemical properties, e.g. spectroscopic, surface, solution or solid state characteristics, the physical aspects of their preparation, e.g. precipitation, nucleation and growth, crystal formation, liquid crystalline characteristics, their photochemical, ecological or biological properties and the relationship between colour and chemical constitution. However, papers are considered which deal with the more fundamental aspects of colourant application and of the interactions of colourants with substrates or media. The journal will interest a wide variety of workers in a range of disciplines whose work involves dyes, pigments and their intermediates, and provides a platform for investigators with common interests but diverse fields of activity such as cosmetics, reprographics, dye and pigment synthesis, medical research, polymers, etc.