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


School of Pharmacy, Jinan University, Guangzhou City Key Laboratory of Precision Chemical Drug Development, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development, Ministry of Education (MOE) of People's Republic of China, 601 Huangpu Avenue West, Guangzhou, 510632, China. [Email]


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 α,β-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.