ArticleMolecular & cellular proteomics : MCP2019
Quantitative Multiplex Substrate Profiling of Peptidases by Mass Spectrometry.
Article in Molecular & cellular proteomics : MCP, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- mspms: an R package and GUI for multiplex substrate profiling by mass spectrometry.BMC bioinformatics · 2026Article
- Substrate profiling of marine-derived thermotolerant cysteine protease reveals unique cleavage preferences for industrial applications.Scientific reports · 2025Article
- Enhancing schistosomiasis drug discovery approaches with optimized proteasome substrates.Protein science : a publication of the Protein Society · 2025Article
- Conserved specificity of extracellular wastewater peptidases revealed by multiplex substrate profiling by mass spectrometry.Environmental chemistry letters · 2025Article
- Distinct substrate specificities of the three catalytic subunits of the Trichomonas vaginalis proteasome.Protein science : a publication of the Protein Society · 2024Article
- Deep quantification of substrate turnover defines protease subsite cooperativity.Molecular systems biology · 2024Article
- Plant and Arthropod IgE-Binding Papain-like Cysteine Proteases: Multiple Contributions to Allergenicity.Foods (Basel, Switzerland) · 2024Review
- In-Depth Specificity Profiling of Endopeptidases Using Dedicated Mix-and-Split Synthetic Peptide Libraries and Mass Spectrometry.Analytical chemistry · 2023Article
- Chemical Blockage of the Mitochondrial Rhomboid Protease PARL by Novel Ketoamide Inhibitors Reveals Its Role in PINK1/Parkin-Dependent Mitophagy.Journal of medicinal chemistry · 2023Article
- Multiplex substrate profiling by mass spectrometry for proteases.Methods in enzymology · 2023Article
- The human pathobiontProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cathepsin B Dipeptidyl Carboxypeptidase and Endopeptidase Activities Demonstrated across a Broad pH Range.Biochemistry · 2022Article
- Making the cut with protease engineering.Cell chemical biology · 2022Review
- Molecular Features of CA-074 pH-Dependent Inhibition of Cathepsin B.Biochemistry · 2022Article
- Inhibition of Serine Proteases as a Novel Therapeutic Strategy for Abdominal Pain in IBS.Frontiers in physiology · 2022Review
- In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET.ACS central science · 2021Article
- Selective Neutral pH Inhibitor of Cathepsin B Designed Based on Cleavage Preferences at Cytosolic and Lysosomal pH Conditions.ACS chemical biology · 2021Article
- Differential Neuropeptidomes of Dense Core Secretory Vesicles (DCSV) Produced at Intravesicular and Extracellular pH Conditions by Proteolytic Processing.ACS chemical neuroscience · 2021Article
- Platform to Discover Protease-Activated Antibiotics and Application to Siderophore-Antibiotic Conjugates.Journal of the American Chemical Society · 2020Article
- The Pseudomonas aeruginosa protease LasB directly activates IL-1β.EBioMedicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Proteolysis is an integral component of life and has been implicated in many disease processes. To improve our understanding of peptidase function, it is imperative to develop tools to uncover substrate specificity and cleavage efficiency. Here, we combine the quantitative power of tandem mass tags (TMTs) with an established peptide cleavage assay to yield quantitative Multiplex Substrate Profiling by Mass Spectrometry (qMSP-MS). This assay was validated with papain, a well-characterized cysteine peptidase, to generate cleavage efficiency values for hydrolysis of 275 unique peptide bonds in parallel. To demonstrate the breath of this assay, we show that qMSP-MS can uncover the substrate specificity of minimally characterized intramembrane rhomboid peptidases, as well as define hundreds of proteolytic activities in complex biological samples, including secretions from lung cancer cell lines. Importantly, our qMSP-MS library uses synthetic peptides whose termini are unmodified, allowing us to characterize not only endo- but also exo-peptidase activity. Each cleaved peptide sequence can be ranked by turnover rate, and the amino acid sequence of the best substrates can be used for designing fluorescent reporter substrates. Discovery of peptide substrates that are selectively cleaved by peptidases which are active at the site of disease highlights the potential for qMSP-MS to guide the development of peptidase-activating drugs for cancer and infectious disease.
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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.