Proteins are the direct executors of life processes, involved in metabolism, signal transduction, gene expression, protein synthesis, transport, and degradation, among others. Their functions within living cells often require precise spatiotemporal control, and any disruption can lead to severe diseases. The main techniques used for proteome profiling are enzyme-catalyzed labeling methods, such as APEX and BioID, which have limitations such as low time resolution and complex operations. Moreover, these methods are only limited to cells that are easy to genetic transfection, while hard-to-transfect cells, primary and clinical samples are hard to analyze.
To address these issues, we focused on the development and exploration of chemical biological approaches, and developed a bioorthogonal photocatalytic labeling technology. This technique combines the unique advantages of photocatalytic chemistry and bioorthogonal reactions, providing precise spatiotemporal resolution in hard-to-transfect samples. It uses photocatalysts and external light to control the labeling of neighboring proteins in living cells (spatial control by targeting of the photocatalyst, and temporal control by the external light), allowing for in situ analysis and mapping of the proteome. The new generation of the chemical technology for proteomic research is expected to overcome the limitations of current techniques, offering a promising approach to understanding the complex roles of proteins in cellular processes.