Abstract
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.
MeSH terms
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Adenine / analogs & derivatives
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Cell Line, Tumor
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / metabolism
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Humans
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Microscopy, Fluorescence
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Piperidines
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / metabolism
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Protein Kinase Inhibitors / pharmacology
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Proteome* / drug effects
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Pyrazoles / chemistry
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Pyrazoles / metabolism
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Pyrazoles / pharmacology
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Pyrimidines / chemistry
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Pyrimidines / metabolism
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Pyrimidines / pharmacology
Substances
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Piperidines
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Protein Kinase Inhibitors
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Proteome
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Pyrazoles
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Pyrimidines
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ibrutinib
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EGFR protein, human
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ErbB Receptors
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Adenine