Chemistry Seminar Presented by Dr. Nicholas Till

The Department of Chemistry is pleased to host Dr. Nicholas Till for a seminar on Friday, December 13. Title: "Mechanistic Investigation of Nickel/Photoredox Catalysis and Redirecting Trogocytosis for Targeted Protein Transfer" Abstract: Part I: Visible light photoredox catalysis is a powerful method to modulate small molecule and transition metal reactivity, but we lack insight into the mechanistic basis of this technology. I will present a comprehensive study of an industrially important Nickel/photoredox catalyzed C-N cross-coupling reaction. Using a combination of reaction kinetic analysis, ultrafast spectroscopy, and stoichiometric organometallic studies, we elucidate the key steps in the mechanism of this reaction. We then leverage these insights to design a new photocatalyst yielding improved reaction rate (>30-fold) and quantum yield (>10-fold). Part II: Targeted degradation of cell surface proteins can address therapeutic challenges rooted in pathologic over-expression or over-activation of a disease-driving protein. Directly introducing cell surface proteins to address therapeutic challenges rooted in pathologic protein deficiency or dysfunction remains an unsolved challenge. I will present the development of bispecific molecules (TrogoTACs) capable of inducing contactdependent protein transfer between cells by redirecting trogocytosis in a targeted fashion. To accomplish this goal, we designed chimeric antibody-small molecule conjugates with specificity to cell surface proteins displaying mutually exclusive expression on donor and acceptor cell types. The protein transfer process is rapid, requires cell-cell contact, and depends on expression of the receptors targeted by the TrogoTAC. Transferred proteins can then redirect T cell engager cytotoxicity to rewire therapeutic targeting towards otherwise unresponsive cancer cells. Host: Chemistry Department Chemical Biology Series