Chemical Imaging and Proteomics Approaches for Probing Copper and Histidine Biology

Chemistry provides valuable tools to probe and influence the molecular processes in biology. Such processes are made available by both large biomolecules and small molecule species. As an example of a transition metal nutrient, copper plays essential roles in respiration, electron transfer, antioxidant defense and oxidation of metabolites, while aberrant copper homeostasis occurs with severe diseases states including neurodegenerative disorders, diabetes and cancer. On the other side, proteins, as large biomolecules, are composed of simple amino acid building blocks. Histidine is an important amino acid, with its imidazole side chain frequently used at catalytic centers and metal-binding sites. This dissertation summarizes my efforts to probing copper and histidine in their biology contexts. Specifically, a series of copper fluorescent sensors with varying colors were designed for visualizing this metal in cells. For probing histidine, we firstly developed bio-inspired thiophosphorodichloridate reagents for its chemoselective labeling on proteins. The labeling of this amino acid provides a starting point for probing histidine by proteomics methodology. Further optimization of the reagents as well as the protocol enables the profiling of histidine in a proteome context