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开发一种生物直角点击释放反应,用于检测多硫化 (H₂S)

Xidan Tong¹, Jiaxuan Chen¹, Maolin Wang¹

¹State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 211198, P. R. China.

Analytical chemistry

|September 17, 2024

概括

研究人员开发了一种新的点击释放策略,用于高度特定的硫化 (H2S) 生物对角探针. 这种方法可以选择性地检测H2S并研究其生物作用,包括蛋白质S-化.

科学领域:

化学生物学化学生物学
生物有机化学生物有机化学
分子成像学分子成像学

背景情况:

硫化 (H2S) 是一种具有不同生理作用的关键信号分子.
开发用于在生物系统中检测H2S的特定探针仍然是一个挑战.

研究的目的:

为特定的H2S检测设计和合成使用点击释放策略的新型生物对角探针.
为了研究H2S介导蛋白质S-化和相关的氧化还原反应的机制.
建立一个新的工具来研究生物系统中的H2S功能.

主要方法:

合成一个用于点击释放策略的cyclooctyne衍生库.
模型探测器 (CM-CT和QN-RHO-CT) 的开发和描述.
探头QN-RHO-CT用于在活细胞中选择性检测H2S和机械学研究的应用.

主要成果:

在H2S暴露时,从模型探测器CM-CT释放有效的光素 (>80%).
开发了具有良好的水溶性和快速释放动力学的QN-RHO-CT,用于在活细胞中选择性检测H2S.
阐明了点击释放机制,证实了关键中间体的形成,并提供了对H2S介导蛋白质S-过硫化的见解.

结论:

开发的点击释放策略为设计H2S生物直角探头提供了一个高度具体和有效的方法.
探测器QN-RHO-CT是生物环境中H2S实时监测的宝贵工具.
这种方法推进了对H2S信号通路和相关生物过程的研究.

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