Ma Chunhui, Yan Dongling, Hou Peng, Liu Xiangbao, Wang Hao, Xia Chunhui, Li Gang, Chen Song
College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.
Research Institute of Medicine & Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.
Molecules. 2023 Jul 27;28(15):5702. doi: 10.3390/molecules28155702.
The well-known small-molecule biothiols have been used to maintain the normal metabolism of peroxy radicals, forming protein structures, resisting cell apoptosis, regulating metabolism, and protecting the homeostasis of cells in the organism. A large amount of research has found that abnormal levels of the above biothiols can cause some adverse diseases, such as changes in hair pigmentation, a slower growth rate, delayed response, excessive sleep and skin diseases. In order to further investigate the exact intracellular molecular mechanism of biothiols, it is imperative to explore effective strategies for real-time biothiol detection in living systems. In this work, a new near-infrared (NIR) emission fluorescence probe (probe 1) for sensitive and selective detection of biothiols was devised by combining dicyanoisophorone derivatives with the dinitrobenzenesulfonyl (DNBS) group. As expected, probe 1 could specifically detect biothiols (Cys, Hcy and GSH) through the dinitrobenzenesulfonyl group to form dye 2, which works as a signaling molecule for sensing biothiols in real samples. Surprisingly, probe 1 showed superior sensing characteristics and low-limit detection towards biothiols (36.0 nM for Cys, 39.0 nM for Hcy and 48.0 nM for GSH) with a large Stokes shift (134 nm). Additionally, the function of probe 1 as a platform for detecting biothiols was confirmed by confocal fluorescence imaging of biothiols in MCF-7 cells and zebrafish. More importantly, the capability of probe 1 in vivo has been further evaluated by imaging the overexpressed biothiols in tumor tissue. It is reasonable to believe that probe 1 can provide a valuable method to explore the relationship between biothiols and the genesis of tumor.
著名的小分子生物硫醇已被用于维持过氧自由基的正常代谢、形成蛋白质结构、抵抗细胞凋亡、调节新陈代谢以及保护机体细胞的稳态。大量研究发现,上述生物硫醇水平异常会引发一些不良疾病,如毛发色素沉着变化、生长速度减慢、反应迟缓、嗜睡和皮肤病等。为了进一步探究生物硫醇确切的细胞内分子机制,探索在活体系统中实时检测生物硫醇的有效策略势在必行。在这项工作中,通过将二氰基异佛尔酮衍生物与二硝基苯磺酰基(DNBS)基团相结合,设计出了一种用于灵敏且选择性检测生物硫醇的新型近红外(NIR)发射荧光探针(探针1)。正如预期的那样,探针1可通过二硝基苯磺酰基特异性检测生物硫醇(半胱氨酸、同型半胱氨酸和谷胱甘肽),形成染料2,其作为一种信号分子用于检测实际样品中的生物硫醇。令人惊讶的是,探针1对生物硫醇表现出卓越的传感特性和低限检测能力(半胱氨酸为36.0 nM,同型半胱氨酸为39.0 nM,谷胱甘肽为48.0 nM),且具有大斯托克斯位移(134 nm)。此外,通过对MCF - 7细胞和斑马鱼中的生物硫醇进行共聚焦荧光成像,证实了探针1作为检测生物硫醇平台的功能。更重要的是,通过对肿瘤组织中过表达的生物硫醇进行成像,进一步评估了探针1在体内的能力。有理由相信,探针1能够为探索生物硫醇与肿瘤发生之间的关系提供一种有价值的方法。