Development of a new protein labeling strategy, oxidation labeling. part 1: Preliminary evaluation and synthesis of tautomycin containing a metal coordinating unit

In the current work we present our preliminary evaluation of a new protein labeling strategy, namely oxidation labeling. We found that a bis(2-picolyl) amine analogue coordinating Cu+ was able to oxidize histidine to oxo-histedine in a small peptide by generating reactive oxygen species upon exposure to hydrogen peroxide. The bis(2-picolyl) amine unit was then incorporated into the natural product tautomycin via an oxime linker. The compound, which showed good activity toward protein phosphatase 1γ (PP1γ), will be used in oxidation labeling studies with PP1γ.