Applications of Activity‐Based Protein Profiling (ABPP) and Bioimaging in Drug Discovery

Abstract

Activity-based protein profiling (ABPP) and bioimaging have been developed in recent years as powerful technologies in drug discovery.S pecifically,b oth approaches can be applied in critical steps of drug development,s uch as therapy target discovery,h igh-throughput drug screening and target identificationo fb ioactive molecules. We have been focusedo nt he development of various strategies that enable simultaneous activity-based protein profiling and bioimagings tudies, thus facilitating an understandingo fd rug actions and potentialt oxicities.I nt his Minireview,w es ummarize these novel strategies and applications,w ith the aim of promoting these technologiesind rug discovery.[a] J. Figure 5. Structures of activity-based probes( ABPs) for target identification and parent inhibitors originating from natural products.

Recent advances in construction of small molecule-based fluorophore-drug conjugates

“…Upon covalent reaction with Btk protein, fluorescence of 5 was immediately switched on due to interruption of intracellular photoinduced electron transfer (PET), allowing real-time imaging of endogenous Btk expression in live cells. Moreover, this conjugate has an alkyne handle capable of being used as an activity-based probe for subsequently target enrichment and identification [ 33 ]. Moreover, our group has presented a series of imaging conjugates, based on SP600125 (a non-covalent inhibitor of c-Jun N-terminal kinases (JNKs)), by using two-step labeling with biorthogonal reporter tags [ 34 ].…”

Capture and Identification of Dual Specificity Mitogen-Activated Protein Kinase Kinase 7 as a Direct Proteomic Target of Berberine to Affect the c-JunN-Terminal Kinase Pathway

“…Furthermore, several direct proteomic targets of BBR, such as NEK7, UHRF1, RXRα, actin and ephrin-B2, 18,24,25,28,29 have been identified to explain its synergistic effects. 24,30,31 The JNK pathway is mainly activated by various damage associated molecular patterns (DAMPs) including proinflammatory cytokines (tumor necrosis factor (TNF)-α and IL-1α), and the stimulation of JNK pathway gives rise to a marked increase of JNK phosphorylation (p-JNK) level, which lead to the progression of inflammatory, neurodegenerative and cell proliferative related diseases. 12,15,25,26 It is worth noting that BBR could suppress p-JNK to alleviate inflammation-related symptoms, such as obesity, insulin resistance, and exert effects on tumorous and neurodegenerative diseases.…”

Photocontrollable Probes for Mitochondrial Protein Profiling

“…It have used to interpret the functions of enzymes, drug on/off-targets, the post-translational modifications of proteins and the molecular mechanism in different cellular physiologies. [10][11][12] Hamachi and coworkers first reported a set of chemical probes (MRMs), containing a mitochondrial localizable motif and various reactive moieties, for mitochondrial proteomics. MRMs were used in cultured cells, primary neurons, and brain slices.…”

“…It has been emerged as a prominent tool to elucidate the organization of cellular proteome by assistance with MS‐based proteome techniques. It have used to interpret the functions of enzymes, drug on/off‐targets, the post‐translational modifications of proteins and the molecular mechanism in different cellular physiologies [10–12] . Hamachi and coworkers first reported a set of chemical probes (MRMs), containing a mitochondrial localizable motif and various reactive moieties, for mitochondrial proteomics.…”