"Small Molecule Tuning of Cellular Sulfur Transfer"
Maintenance of redox homeostasis is essential for cellular survival and growth. Small gaseous entities which are reactive biological species derived from oxygen, nitrogen as well as sulfur are generated and quenched during these processes. These small gaseous molecules mediate a number of cellular processes and signaling events. The major challenges in this field include reliable detection, controlled generation as well as inhibition of biosynthesis of these species. Our lab works on developing tools to study these complex biological processes in a systematic manner. Using fundamental and mechanistic organic chemistry as the basis, we design and develop small molecules that can fragment to produce the aforementioned species. For example, protein persulfidation, a key cellular sulfur transfer process in cells, has emerged as a key player in biological sulfur metabolism as well as a cytoprotective mechanism with implications in mitigating stress associated with neurodegenerative disorders, inflammation and cardiovascular conditions. This underscores the importance of the controlled generation of persulfides within cells. Our laboratory has developed new strategies for enhancing persulfides within cells. Incorporation of stimuli responsive triggers facilitate site-directed generation of persulfides. In addition, we have also developed unnatural substrates for a transferase that enables tracking sulfur that is transferred through this major persulfidation enzyme. Together, the toolbox developed by us permits the systematic study of sulfur redox biology and holds great promise for selective and reliable enhancement of cellular persulfides for therapeutic applications.
~ Coffee/tea will be served prior to lecture~