When
Presenter:
Nick Kuehl
Ph.D. Candidate, Chemistry & Biochemistry, University of Arizona
Abstract:
The synthetic modification of biomolecules has provided remarkable advances toward understanding cellular phenomena and developing therapeutics. Given the complexity of biomolecules, developing methods that selectively label biomolecules has proven challenging. This talk will focus on how pyridinium and quinolinium salt derivatives can be harnessed for protein and peptide modification. This research aimed to address two important questions: 1) what non-covalent interactions between biomolecules and reagent scaffolds can we use to enhance labeling selectivity and 2) How can diversifying connectivity within these scaffolds provide new reagents for biomolecular modification? These research questions were addressed by synthesizing a variety of novel pyridinium and quinolinium salt derivatives followed by analysis of their reactivity with peptides and proteins.
First, I will describe how N-carbamoyl pyridinium salts photochemically and selectively transfer N-carbamoyl groups to tryptophan. I will present how these pyridiniums were developed for milligram-scale peptide modification and chemical proteomic workflows. Next, I will discuss the development of cationic aromatic sulfonate ester photocages and their use in rapid biomolecular trifluoromethylation using visible light. These photocages were used in protein mapping experiments and milligram scale peptide trifluoromethylation at aromatic amino acid residues. Finally, I will present the development of cationic aromatic esters for synthetic biomolecular acylation harnessing non-covalent interactions. In total, this research has provided novel updates to biomolecular modification by harnessing non-covalent interactions and adapting scaffolds for labeling using various mechanistic pathways.