ArticleChemical science2020
Engineered unnatural ubiquitin for optimal detection of deubiquitinating enzymes.
Article in Chemical science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Advances in the chemical synthesis of human proteoforms.Science China. Life sciences · 2025Review
- OTUD1 Deficiency Alleviates LPS-Induced Acute Lung Injury in Mice by Reducing Inflammatory Response.Inflammation · 2025Article
- Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.Nature communications · 2025Article
- Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.bioRxiv : the preprint server for biology · 2024Article
- Ubiquitin-Derived Fragment as a Peptide Linker for the Efficient Cleavage of a Target Protein from a Degron.ACS chemical biology · 2024Article
- Mass spectrometric assays monitoring the deubiquitinase activity of the SARS-CoV-2 papain-like protease inform on the basis of substrate selectivity and have utility for substrate identification.Bioorganic & medicinal chemistry · 2023Article
- Non-Canonical Amino Acids in Analyses of Protease Structure and Function.International journal of molecular sciences · 2023Review
- Design and Synthesis of Ubiquitin-Based Chemical Tools with Unnatural Amino Acids for Selective Detection of Deubiquitinases.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Rational Development and Characterization of a Ubiquitin Variant with Selectivity for Ubiquitin C-Terminal Hydrolase L3.Biomolecules · 2022Article
- Synthesis and Evaluation of Ubiquitin-Dioxetane Conjugate as a Chemiluminescent Probe for Monitoring Deubiquitinase Activity.Bioconjugate chemistry · 2021Article
- Exploring the Versatility of the Covalent Thiol-Alkyne Reaction with Substituted Propargyl Warheads: A Deciding Role for the Cysteine Protease.Journal of the American Chemical Society · 2021Article
- SARS-CoV-2 Papain-Like Protease Potential Inhibitors-In Silico Quantitative Assessment.International journal of molecular sciences · 2021Article
- Targeting SARS-CoV-2 Proteases for COVID-19 Antiviral Development.Frontiers in chemistry · 2021Review
- Activity profiling and crystal structures of inhibitor-bound SARS-CoV-2 papain-like protease: A framework for anti-COVID-19 drug design.Science advances · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Deubiquitinating enzymes (DUBs) are responsible for removing ubiquitin (Ub) from its protein conjugates. DUBs have been implicated as attractive therapeutic targets in the treatment of viral diseases, neurodegenerative disorders and cancer. The lack of selective chemical tools for the exploration of these enzymes significantly impairs the determination of their roles in both normal and pathological states. Commercially available fluorogenic substrates are based on the C-terminal Ub motif or contain Ub coupled to a fluorophore (Z-LRGG-AMC, Ub-AMC); therefore, these substrates suffer from lack of selectivity. By using a hybrid combinatorial substrate library (HyCoSuL) and a defined P2 library containing a wide variety of nonproteinogenic amino acids, we established a full substrate specificity profile for two DUBs-MERS PLpro and human UCH-L3. Based on these results, we designed and synthesized Ub-based substrates and activity-based probes (ABPs) containing selected unnatural amino acids located in the C-terminal Ub motif. Biochemical analysis and cell lysate experiments confirmed the activity and selectivity of engineered Ub-based substrates and probes. Using this approach, we propose that for any protease that recognizes Ub and Ub-like substrates, a highly active and selective unnatural substrate or probe can be engineered.
Identifiers
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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.