SMALL CHEMICAL TAGS FOR PROTEIN PROFILING AND LIVE-CELL IMAGING OF SMALL MOLECULES

Abstract

Target engagement and target identification are two important aspects of studying small-molecule drug in living systems, which are usually carried out with chemical probes using different approaches. Our current studies described novel, useful and small chemical tags that allow facile preparation of high-quality chemical probes with dual capabilities of in situ protein profiling and live-cell imaging. For the first project, a set of new minimalist diazirine photo-crosslinkers were developed based on the recently reported copper-free bioorthogonal reactions. These linkers were applied to conveniently convert a small molecule into an affinity-based probe, which upon photo- activation covalently label cellular targets to facilitate subsequent studies. The second project focused on the design of novel reaction-based fluorescent sensors based on the phosphotyrosine residue, which achieved simultaneous live-cell imaging and target labeling. This probe could be used as the core recognition unit targeting protein tyrosine phosphatases and other phosphotyrosine binding proteins.