CELL-BASED PROTEOME PROFILING OF BIOACTIVE COMPOUNDS: EXPANSION AND NEW CONCEPTS

Abstract

Bioorthogonal chemistry and cell-based chemical proteomics have been widely applied in drug discovery and target validation of bioactive compounds. In the first project, different bioorthogonal tags were introduced to lipid precursor, which upon metabolic incorporation allow for lipid imaging. In the second project, photo affinity-based proteome profiling was exploited to investigate lipid–protein interaction. This led to the identification of thousands of lipid-interacting proteins, including several new proteins that have not been identified before. In the third project, reactive oxygen species (ROS) detection-based phenotypic screening was used to find the potent chalcone compound that has anti-cancer activity. Activity-based protein profiling (ABPP) was further applied to identify the target protein of the hit compound. The hit compound was also used to delineate the biochemical and cellular functions of enzymes.