Dissertation
NOVEL THIOL BLOCKING REAGENTS AND THEIR APPLICATION
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2022
DOI:
https://doi.org/10.7273/000004360
Handle:
https://hdl.handle.net/2376/118841
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).
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Details
- Title
- NOVEL THIOL BLOCKING REAGENTS AND THEIR APPLICATION
- Creators
- Jessica Renee Knight
- Contributors
- Ming Xian (Advisor)Clifford E Berkman (Advisor)Gregory Crouch (Committee Member)Qiang Zhang (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Chemistry, Department of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 114
- Identifiers
- 99900883036101842
- Language
- English
- Resource Type
- Dissertation