A Sweet H_2S/H_2O_2 Dual Release System and Specific Protein S-Persulfidation Mediated by Thioglucose/Glucose Oxidase

摘要

H_2S and H_2O_2 are two redox regulating molecules that play important roles in many physiological and pathological processes. While each of them has distinct biosynthetic pathways and signaling mechanisms, the crosstalk between these two species is also known to cause critical biological responses such as protein S-persulfidation. So far, many chemical tools for the studies of H_2S and H_2O_2 have been developed, such as the donors and sensors for H_2S and H_2O_2. However, these tools are normally targeting single species (e.g., only H_2S or only H_2O_2). As such, the crosstalk and synergetic effects between H_2S and H_2O_2 have hardly been studied with those tools. In this work, we report a unique H_2S/H_2O_2 dual donor system by employing 1-thio-β-D-glucose and glucose oxidase (GOx) as the substrates. This enzymatic system can simultaneously produce H_2S and H_2O_2 in a slow and controllable fashion, without generating any bio-unfriendly byproducts. This system was demonstrated to cause efficient S-persulfidation on proteins. In addition, we expanded the system to thiolactose and thioglucose-disulfide; therefore, additional factors (β-galactosidase and cellular reductants) could be introduced to further control the release of H_2S/H_2O_2. This dual release system should be useful for future research on H_2S and H_2O_2.