ArticleJournal of the American Chemical Society2019
Monitoring the Immunoproteasome in Live Cells Using an Activity-Based Peptide-Peptoid Hybrid Probe.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- From probe to prodrug: immunoproteasome activity as a trigger for disease-selective therapeutics.Signal transduction and targeted therapy · 2026Article
- Article
- Synthesis and Application of a Versatile Immunoproteasome Activity Probe.Chembiochem : a European journal of chemical biology · 2024Article
- Synthesis and Application of a Caged Bioluminescent Probe for the Immunoproteasome.Current protocols · 2024Article
- Caged aminoluciferin probe for bioluminescent immunoproteasome activity analysis.RSC chemical biology · 2024Article
- Primed for Interactions: Investigating the Primed Substrate Channel of the Proteasome for Improved Molecular Engagement.Molecules (Basel, Switzerland) · 2024Review
- Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications.Current medicinal chemistry · 2024Review
- 20S proteasome hydrolysis of LLVY substrates to determine preferences for moieties in its primed substrate channel.Bioorganic & medicinal chemistry letters · 2023Article
- Methods for the discovery of small molecules to monitor and perturb the activity of the human proteasome.Future medicinal chemistry · 2021Review
- Multiplexed Enzyme Activity-Based Probe Display via Hybridization.ACS combinatorial science · 2020Article
- Fluorescent Probes with Unnatural Amino Acids to Monitor Proteasome Activity in Real-Time.ACS chemical biology · 2020Article
- Assessing the range of enzymatic and oxidative tunability for biosensor design.Journal of materials chemistry. B · 2020Review
- Immunoproteasome in IgA Nephropathy: State-of-Art and Future Perspectives.International journal of biological sciences · 2020Review
- Synthesis and Application of an Activity-Based Peptide-Peptoid Hybrid Probe for the Immunoproteasome.Current protocols in chemical biology · 2019Article
- Methods to Discover and Evaluate Proteasome Small Molecule Stimulators.Molecules (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Activity-based probes have greatly improved our understanding of the intrinsic roles and expression levels of various proteins within cells. To be useful in live cells, probes must be cell permeable and provide a read-out that can be measured without disrupting the cells or the activity of the target. Unfortunately, probes for the various forms of the proteasome that can be utilized in intact cells are limited; commercially available probes are most effectively used with purified protein or cell lysate. The proteasome, both the 26S and various isoforms of the 20S CP, is an important target with reported roles in cancer, autoimmune disorders, and neurodegenerative diseases. Here, we present the development of a selective probe for the immunoproteasome, a specialized isoform of the 20S proteasome, that becomes expressed in cells that encounter an inflammatory signal. Using a one-bead, one-compound library of small peptides, we discovered a trimer sequence efficiently cleaved by the immunoproteasome with significant selectivity over the standard proteasome. Upon conjugating this sequence to rhodamine 110 and a peptoid, we generated a probe with a considerable improvement in sensitivity compared to that of current aminomethylcoumarin-based proteasome probes. Importantly, our probe was capable of labeling immunoproteasome-expressing cells while maintaining its selectivity over other cellular proteases in live cell cultures. We anticipate this probe to find wide utility for those that wish to study the immunoproteasome's activity in a variety of cell lines and to be used as a reporter to discover small molecules that can perturb the activity of this proteasome isoform.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.