Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity

Zhiming Cheng; Emily J Thompson; Lorena Mendive-tapia; Jamie I Scott; Sam Benson; Takanori Kitamura; Ana Senan-salinas; Youhani Samarakoon; Edward W Roberts; Maykel A. Arias; Julian Pardo; Eva M Galvez; Marc Vendrell

doi:10.1002/anie.202216142

Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity

Zhiming Cheng, Emily J Thompson, Lorena Mendive-tapia, Jamie I Scott, Sam Benson, Takanori Kitamura, Ana Senan-salinas, Youhani Samarakoon, Edward W Roberts, Maykel A. Arias, Julian Pardo, Eva M Galvez, Marc Vendrell

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Journal	Angewandte Chemie International Edition
Early online date	23 Dec 2022
DOIs	https://doi.org/10.1002/anie.202216142
Publication status	E-pub ahead of print - 23 Dec 2022

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10.1002/anie.202216142Licence: Creative Commons: Attribution (CC-BY)

Angew Chem Int Ed - 2022 - Cheng - Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune CellFinal published version, 896 KBLicence: Creative Commons: Attribution (CC-BY)

https://onlinelibrary.wiley.com/doi/10.1002/anie.202216142

Dynamic Activatable Fluorophores
Vendrell Escobar, M.
EU government bodies
1/06/18 → 31/05/23
Project: Research

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Cheng, Z., Thompson, E. J., Mendive-tapia, L., Scott, J. I., Benson, S., Kitamura, T., Senan-salinas, A., Samarakoon, Y., Roberts, E. W., Arias, M. A., Pardo, J., Galvez, E. M., & Vendrell, M. (2022). Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity. Angewandte Chemie International Edition. Advance online publication. https://doi.org/10.1002/anie.202216142

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title = "Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity",

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.",

author = "Zhiming Cheng and Thompson, {Emily J} and Lorena Mendive-tapia and Scott, {Jamie I} and Sam Benson and Takanori Kitamura and Ana Senan-salinas and Youhani Samarakoon and Roberts, {Edward W} and Arias, {Maykel A.} and Julian Pardo and Galvez, {Eva M} and Marc Vendrell",

year = "2022",

month = dec,

day = "23",

doi = "10.1002/anie.202216142",

language = "English",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

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TY - JOUR

T1 - Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity

AU - Cheng, Zhiming

AU - Thompson, Emily J

AU - Mendive-tapia, Lorena

AU - Scott, Jamie I

AU - Benson, Sam

AU - Kitamura, Takanori

AU - Senan-salinas, Ana

AU - Samarakoon, Youhani

AU - Roberts, Edward W

AU - Arias, Maykel A.

AU - Pardo, Julian

AU - Galvez, Eva M

AU - Vendrell, Marc

PY - 2022/12/23

Y1 - 2022/12/23

N2 - 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.

AB - 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.

U2 - 10.1002/anie.202216142

DO - 10.1002/anie.202216142

M3 - Article

SN - 1433-7851

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

ER -

Fluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity

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Dynamic Activatable Fluorophores

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