A Sweet H₂S/H₂O₂ Dual Release System and Specific Protein S-Persulfidation Mediated by Thioglucose/Glucose Oxidase

H₂S and H₂O₂ 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 H₂S and H₂O₂ have been developed, such as the donors and sensors for H₂S and H₂O₂. However, these tools are normally targeting single species (e.g., only H₂S or only H₂O₂). As such, the crosstalk and synergetic effects between H₂S and H₂O₂ have hardly been studied with those tools. In this work, we report a unique H₂S/H₂O₂ dual donor system by employing 1-thio-β-d-glucose and glucose oxidase (GOx) as the substrates. This enzymatic system can simultaneously produce H₂S and H₂O₂ 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 H₂S/H₂O₂. This dual release system should be useful for future research on H₂S and H₂O₂.