Minimalist linkers suitable for irreversible inhibitors in simultaneous proteome profiling, live-cell imaging and drug screening

Activity-based protein profiling (ABPP) and bioimaging have been powerful approaches for in situ drug screening and target identification. However, these approaches are still hindered by the preparation of high-quality probes. To address this challenge, we developed a series of novel minimalist linkers for irreversible inhibitors by incorporation of various bioorthogonal handles into an alpha,beta-unsaturated amide, a common moiety of many irreversible inhibitors. The linker containing probes have been demonstrated to be suitable for simultaneous protein labelling, live cell imaging and drug screening.