A Sweet HS/HO Dual Release System and Specific Protein S-Persulfidation Mediated by Thioglucose/Glucose Oxidase.

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