Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems.

Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems.
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DOI:
10.1039/c4cs00298a
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发表时间:
2015-07-21
影响因子:
46.2
通讯作者:
Chang CJ
Chang CJ
中科院分区:
化学1区
文献类型:
--
作者:
Lin VS;Chen W;Xian M;Chang CJ

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硫化氢(H2S)是由细菌和高等真核生物(包括哺乳类脊椎动物)产生的气体种类,近年来因其对人类健康和疾病的贡献而引起关注。H2S已被提出作为许多组织类型中的细胞保护剂和气体递质,包括介导血管中的血管张力以及脑中的神经调节。决定H2S如何影响细胞信号传导和其他生理事件的分子机制仍然没有得到充分的理解。此外,H2S参与金属结合相互作用和形成相关的RSS,如硫烷硫可能有助于其他不同的信号传导途径。由于其广泛的生物学作用和独特的化学性质,H2S是化学生物学方法的一个有吸引力的目标,以阐明其生产,运输和下游功能。在这种情况下,基于反应的荧光探针提供了一套通用的筛选工具,以可视化H2S池在生活系统。用于H2S检测的分子探针开发中使用的三种主要策略包括叠氮化物和硝基还原、亲核攻击和CuS沉淀。这些方法中的每一种都利用H2S的强亲核性和还原效力来实现优于其他生物硫醇的选择性。此外,已经开发了多种方法用于检测其他反应性硫物质(RSS),包括亚硫酸盐和亚硫酸氢盐,以及硫烷硫物质和相关修饰,如S-亚硝基硫醇。访问这个不断增长的化学工具箱的新分子探针H2S和相关的RSS设置阶段,应用这些发展中的技术来探测活性硫生物学在生活系统中。
Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploit the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.
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