When
Location:
Manuel Pacheco Integrated Learning Center, Room 130
Presenter:
Nick Kuehl, Graduate Student, Chemistry and Biochemistry, The University of Arizona
Abstract:
The ability to decorate and assemble biomolecules to probe and/or manipulate biological systems has resulted in remarkable advances in modern medicine. This bioconjugate “toolbox” has enabled the unveiling of endogenous cellular events and has been utilized to develop new therapeutic modalities.
Many elegant methods, targeting various biochemical motifs, have been developed to construct bioconjugates, yet a persistent need for new and/or improved techniques exists. In this talk, I will highlight the ways in which we are contributing to this effort through the development of pyridinium and quinolinium derivatives that modify proteins in a selective manner using both thermo- and photochemical methods. The overarching theme of the research talk is how diversifying connectivity and functionality of a single molecular scaffold can result in a manifold increase in utility as a group transfer reagent.
First, I will describe how pyridinium salt scaffolds, utilizing photochemical initiated electron-transfer, selectively deliver N-carbamoyl groups to Tryptophan and have been used for peptide modification and chemoproteomic workflows. Next, I will discuss the use of quinolinium sulfonate ester photocages for the rapid release of sulfonyl radicals. These quinoliniums have been derivatized to be a source of the trifluoromethyl radical and used for protein mapping experiments and peptide trifluoromethylation at aromatic amino acid residues. Finally, I will describe another family of quinolinium derivatives that are being developed to selectively deliver acyl groups to peptides and proteins by utilizing non-covalent interactions.