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Fluorogenic Granzyme A Substrates Enable Real-Time Imaging of Adaptive Immune Cell Activity |
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| Authors: | Zhiming Cheng Dr Emily J Thompson Dr Lorena Mendive-Tapia Dr Jamie I Scott Dr Sam Benson Dr Takanori Kitamura Ana Senan-Salinas Dr Youhani Samarakoon Dr Edward W Roberts Dr Maykel A Arias Prof Dr Julian Pardo Dr Eva M Galvez Prof Dr Marc Vendrell |
| Institution: | 1. Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK;2. MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, UK;3. Instituto de Carboquimica, CSIC, Zaragoza, Spain;4. Cancer Research UK Beatson Institute, Glasgow, UK;5. CIBERINFEC, Instituto de Salud Carlos III, Zaragoza, Spain
Aragón Health Research Institute, Biomedical Research Centre of Aragón and Dpt of Microbiology, Preventive Medicine and Public Health, Zaragoza, Spain;6. Instituto de Carboquimica, CSIC, Zaragoza, Spain CIBERINFEC, Instituto de Salud Carlos III, Zaragoza, Spain |
| Abstract: | Cytotoxic immune cells, including T lymphocytes (CTLs) and natural killer (NK) cells, are essential components of the host response against tumors. CTLs and NK cells secrete granzyme A (GzmA) upon recognition of cancer cells; however, there are very few tools that can detect physiological levels of active GzmA with high spatiotemporal resolution. Herein, we report the rational design of the near-infrared fluorogenic substrates for human GzmA and mouse GzmA. These activity-based probes display very high catalytic efficiency and selectivity over other granzymes, as shown in tissue lysates from wild-type and GzmA knock-out mice. Furthermore, we demonstrate that the probes can image how adaptive immune cells respond to antigen-driven recognition of cancer cells in real time. |
| Keywords: | Cancer Fluorescence Hemicyanine Peptides Probes |