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线粒体靶向、环境敏感的红色荧光探针用于含毗邻二硫键蛋白的高灵敏检测和成像。

Mitochondrion-Targeting, Environment-Sensitive Red Fluorescent Probe for Highly Sensitive Detection and Imaging of Vicinal Dithiol-Containing Proteins.

机构信息

Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University , Changsha 410082, P. R. China.

出版信息

Anal Chem. 2017 Nov 7;89(21):11203-11207. doi: 10.1021/acs.analchem.7b03724. Epub 2017 Oct 25.

Abstract

Mitochondrial vicinal dithiol-containing proteins (VDPs) are key regulators in cellular redox homeostasis and useful markers for diagnostics of redox-dependent diseases. Current probes fail to target mitochondrial VDPs and show limited sensitivity and response rate. We develop a novel fluorescent probe using an engineered benzoxadiazole fluorophore that allows selective targeting of mitochondria and exhibits highly sensitive environment responsiveness. This probe is almost nonfluorescent in aqueous media, while delivering intense fluorescence upon binding to VDPs via a cyclic dithiaarsane ligand. The fluorescence probe is shown to have rapid response within 30 s and high sensitivity for detecting reduced bovine serum albumin (rBSA) in the concentration range from 0 to 0.1 μM with a detection limit of 2 nM. To our knowledge, this is the first fluorescence probe for VDPs which exhibits deep red emission, instantaneous response, high turn-on fluorescence ratio, and specific mitochondrial localization. It may provide a new tool for in situ monitoring mitochondrial VDPs.

摘要

线粒体毗邻二硫醇含蛋白(VDPs)是细胞氧化还原平衡的关键调节剂,也是氧化还原依赖性疾病诊断的有用标志物。目前的探针无法靶向线粒体 VDPs,并且表现出有限的灵敏度和响应速率。我们使用经过工程设计的苯并恶二唑荧光团开发了一种新型荧光探针,该探针允许选择性靶向线粒体,并表现出高度敏感的环境响应性。该探针在水介质中几乎没有荧光,而在通过环状二硫代胂配体与 VDPs 结合时则发出强烈的荧光。该荧光探针在 30 秒内即可快速响应,并且能够以 2 nM 的检测限在 0 至 0.1 μM 的浓度范围内检测到还原型牛血清白蛋白(rBSA),灵敏度很高。据我们所知,这是第一个显示深红色发射、瞬时响应、高开启荧光比和特异性线粒体定位的 VDPs 荧光探针。它可能为原位监测线粒体 VDPs 提供一种新工具。

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