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

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

Authors :
Cheng Z
Thompson EJ
Mendive-Tapia L
Scott JI
Benson S
Kitamura T
Senan-Salinas A
Samarakoon Y
Roberts EW
Arias MA
Pardo J
Galvez EM
Vendrell M
Source :
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Feb 13; Vol. 62 (8), pp. e202216142. Date of Electronic Publication: 2023 Jan 16.
Publication Year :
2023

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.<br /> (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Details

Language :
English
ISSN :
1521-3773
Volume :
62
Issue :
8
Database :
MEDLINE
Journal :
Angewandte Chemie (International ed. in English)
Publication Type :
Academic Journal
Accession number :
36562327
Full Text :
https://doi.org/10.1002/anie.202216142