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2H-Thiopyran-2-thione sulfine, a compound for converting H2S to HSOH/H2S2 and increasing intracellular sulfane sulfur levels
Nature Communications ( IF 14.7 ) Pub Date : 2024-03-19 , DOI: 10.1038/s41467-024-46652-7
Qi Cui 1 , Meg Shieh 1 , Tony W Pan 1 , Akiyuki Nishimura 2 , Tetsuro Matsunaga 3 , Shane S Kelly 4 , Shi Xu 1 , Minkyung Jung 3 , Seiryo Ogata 3 , Masanobu Morita 3 , Jun Yoshitake 3 , Xiaoyan Chen 1 , Jerome R Robinson 1 , Wei-Jun Qian 4 , Motohiro Nishida 2, 5 , Takaaki Akaike 3 , Ming Xian 1
Affiliation  

Reactive sulfane sulfur species such as persulfides (RSSH) and H2S2 are important redox regulators and closely linked to H2S signaling. However, the study of these species is still challenging due to their instability, high reactivity, and the lack of suitable donors to produce them. Herein we report a unique compound, 2H-thiopyran-2-thione sulfine (TTS), which can specifically convert H2S to HSOH, and then to H2S2 in the presence of excess H2S. Meanwhile, the reaction product 2H-thiopyran-2-thione (TT) can be oxidized to reform TTS by biological oxidants. The reaction mechanism of TTS is studied experimentally and computationally. TTS can be conjugated to proteins to achieve specific delivery, and the combination of TTS and H2S leads to highly efficient protein persulfidation. When TTS is applied in conjunction with established H2S donors, the corresponding donors of H2S2 (or its equivalents) are obtained. Cell-based studies reveal that TTS can effectively increase intracellular sulfane sulfur levels and compensate for certain aspects of sulfide:quinone oxidoreductase (SQR) deficiency. These properties make TTS a conceptually new strategy for the design of donors of reactive sulfane sulfur species.



中文翻译:


2H-Thiopyran-2-thione sulfine,一种将 H2S 转化为 HSOH/H2S2 并增加细胞内硫烷硫水平的化合物



活性硫烷硫物种如过硫化物 (RSSH) 和 H 2 S 2是重要的氧化还原调节剂,与 H 2 S 信号传导密切相关。然而,由于这些物种的不稳定性、高反应性以及缺乏合适的供体来生产它们,对这些物种的研究仍然具有挑战性。在此,我们报道了一种独特的化合物2H -thiopyran-2-thione sulfine (TTS),它可以特异性地将H 2 S转化为HSOH,然后在过量H 2 S存在下转化为H 2 S 2 。同时,反应产物2H-噻喃-2-硫酮(TT)可以被生物氧化剂氧化重新形成TTS。通过实验和计算研究了 TTS 的反应机理。 TTS可以与蛋白质缀合以实现特异性递送,并且TTS和H 2 S的结合导致高效的蛋白质过硫化。当TTS与已建立的H 2 S供体结合应用时,获得H 2 S 2 (或其等价物)的相应供体。基于细胞的研究表明,TTS 可以有效增加细胞内硫烷硫水平并补偿硫化物:醌氧化还原酶 (SQR) 的某些方面的缺陷。这些特性使 TTS 成为设计活性硫烷硫物种供体的新概念策略。

更新日期:2024-03-23
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