ArticleThe Journal of biological chemistry2020
Noninvasive optical detection of granzyme B from natural killer cells with enzyme-activated fluorogenic probes.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Smart Immunomodulating Nanocomposites Enabling on-Demand Solid Tumor Treatment With Quasi-Real-Time Response Monitoring.Advanced healthcare materials · 2026Article
- Non-Canonical Amino Acids in Analyses of Protease Structure and Function.International journal of molecular sciences · 2023Review
- A Genetically Encoded Dark-to-Bright Biosensor for Visualisation of Granzyme-Mediated Cytotoxicity.International journal of molecular sciences · 2023Article
- Chemical Tools to Image the Activity of PAR-Cleaving Proteases.ACS bio & med chem Au · 2023Review
- Smart probes for optical imaging of T cells and screening of anti-cancer immunotherapies.Chemical Society reviews · 2023Review
- Fluorescent Activity-Based Probe To Image and Inhibit Factor XIa Activity in Human Plasma.Journal of medicinal chemistry · 2023Article
- Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Article
- Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity.Angewandte Chemie (International ed. in English) · 2023Article
- Extended cleavage specificities of human granzymes A and K, two closely related enzymes with conserved but still poorly defined functions in T and NK cell-mediated immunity.Frontiers in immunology · 2023Article
- In vivo bioluminescence imaging of granzyme B activity in tumor response to cancer immunotherapy.Cell chemical biology · 2022Article
- Multiparameter Longitudinal Imaging of Immune Cell Activity in Chimeric Antigen Receptor T Cell and Checkpoint Blockade Therapies.ACS central science · 2022Article
- Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy.Biomedicines · 2022Review
- A fluorogenic probe for granzyme B enables in-biopsy evaluation and screening of response to anticancer immunotherapies.Nature communications · 2022Article
- Activatable Fluorophores for Imaging Immune Cell Function.Accounts of chemical research · 2022Review
- Role of Serine Proteases at the Tumor-Stroma Interface.Frontiers in immunology · 2022Review
- Near-Infrared Fluorescent Probes for the Detection of Cancer-Associated Proteases.ACS chemical biology · 2021Review
- A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2021Article
- A Functional Chemiluminescent Probe for in Vivo Imaging of Natural Killer Cell Activity Against Tumours.Angewandte Chemie (International ed. in English) · 2021Article
- Peptidyl Activity-Based Probes for Imaging Serine Proteases.Frontiers in chemistry · 2021Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells are key innate immunity effectors that combat viral infections and control several cancer types. For their immune function, human NK cells rely largely on five different cytotoxic proteases, called granzymes (A/B/H/K/M). Granzyme B (GrB) initiates at least three distinct cell death pathways, but key aspects of its function remain unexplored because selective probes that detect its activity are currently lacking. In this study, we used a set of unnatural amino acids to fully map the substrate preferences of GrB, demonstrating previously unknown GrB substrate preferences. We then used these preferences to design substrate-based inhibitors and a GrB-activatable activity-based fluorogenic probe. We show that our GrB probes do not significantly react with caspases, making them ideal for in-depth analyses of GrB localization and function in cells. Using our quenched fluorescence substrate, we observed GrB within the cytotoxic granules of human YT cells. When used as cytotoxic effectors, YT cells loaded with GrB attacked MDA-MB-231 target cells, and active GrB influenced its target cell-killing efficiency. In summary, we have developed a set of molecular tools for investigating GrB function in NK cells and demonstrate noninvasive visual detection of GrB with an enzyme-activated fluorescent substrate.
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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.