Department of Chemistry and Biochemistry, Materials Science Institute, Institute of Molecular Biology, University of Oregon, Eugene, Oregon.
Antioxid Redox Signal. 2020 Jan 10;32(2):96-109. doi: 10.1089/ars.2019.7841. Epub 2019 Oct 29.
Hydrogen sulfide (HS) is an important biological signaling molecule involved in many physiological processes. These diverse roles have led researchers to develop contemporary methods to deliver HS under physiologically relevant conditions and in response to various stimuli. Different small-molecule donors have been developed that release HS under various conditions. Key examples include donors activated in response to hydrolysis, to endogenous species, such as thiols, reactive oxygen species, and enzymes, and to external stimuli, such as photoactivation and bio-orthogonal chemistry. In addition, an alternative approach to release HS has utilized the catalyzed hydrolysis of carbonyl sulfide (COS) by carbonic anhydrase to generate libraries of activatable COS-based HS donors. Small-molecule HS donors provide important research and pharmacological tools to perturb HS levels. Key needs, both in the development and in the use of such donors, include access to new donors that respond to specific stimuli as well as donors with well-defined control compounds that allow for clear delineation of the impact of HS delivery from other donor byproducts. The abundance of reported small-molecule HS donors provides biologists and physiologists with a chemical toolbox to ask key biological questions and to develop HS-related therapeutic interventions. Further investigation into different releasing efficiencies in biological contexts and a clear understanding of biological responses to donors that release HS gradually (, hours to days) donors that generate HS quickly (, seconds to minutes) is needed.
硫化氢（HS）是一种重要的生物信号分子，参与许多生理过程。这些多样化的作用促使研究人员开发出在生理相关条件下并响应各种刺激的 HS 传递的现代方法。已经开发出不同的小分子供体，可在各种条件下释放 HS。关键示例包括响应水解、内源性物质（如硫醇、活性氧物种和酶）以及外部刺激（如光激活和生物正交化学）而激活的供体。此外，释放 HS 的另一种方法是利用碳酸酐酶催化水解羰基硫（COS）以生成可激活的基于 COS 的 HS 供体库。小分子 HS 供体为扰动 HS 水平提供了重要的研究和药理学工具。在开发和使用此类供体时，都有一些关键需求，包括获得对特定刺激有响应的新型供体，以及具有明确对照化合物的供体，以便清楚地区分 HS 传递与其他供体副产物的影响。已报道的小分子 HS 供体的丰富性为生物学家和生理学家提供了一个化学工具箱，用于提出关键的生物学问题并开发与 HS 相关的治疗干预措施。需要进一步研究在不同的生物背景下释放效率的差异，以及对快速（数秒至数分钟）释放 HS 的供体和逐渐（数小时至数天）释放 HS 的供体产生的生物学反应有更清晰的认识。
