Chemistry PhD Defense – Jessica Knight

About the event

Title: Novel Thiol Blocking Reagents and Their Application

Abstract: Thiols play critical roles in cell biology. These include maintaining redox homeostasis, as well as the modulation and regulation of protein activity. Dysregulation of thiols has been linked to several diseases including diabetes, cancer, and neurodegenerative disease. For this reason, there is a need for tools for the detection and labeling of thiols. Thiol blocking reagents can be used to label and identification of protein thiols. Where thiol-specific fluorescent probes are able to detect and report the presence of thiols in real time in cells. In this work we demonstrated that benzothiazole derived sulfones and sulfoxides are efficient thiol blocking reagents. The reaction between thiol and sulfone derivative produces a sulfinic acid (RSO2H). This could be used to further trigger the release of an -OH containing payload. This was applied to develop a modular template for thiol triggered fluorescent sensors and prodrugs (such as nitric oxide (NO) donor pyrrolidine-NONOate). In optimizing the intramolecular cyclization, we further found the sulfinic acid (RSO2H) can further react with sulfane sulfurs to form thiosulfonic acids (RSO2SH). This was used to design specific sensors for hydrogen polysulfides (H2Sn).