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

Cheng, Zhiming ; Thompson, Emily J ; Mendive-Tapia, Lorena ; Scott, Jamie I ; Benson, Sam ; Kitamura, Takanori ; Senan-Salinas, Ana ; Samarakoon, Youhani ; Roberts, Edward W ; Arias, Maykel A ; Pardo, Julian (Universidad de Zaragoza) ; Galvez, Eva M ; Vendrell, Marc

Resumen: 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.

Idioma: Inglés

DOI: 10.1002/anie.202216142

Año: 2022

Publicado en: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 62, 8 (2022), e202216142 [7 pp.]
ISSN: 1433-7851

Factor impacto JCR: 16.6 (2022)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 13 / 178 = 0.073 (2022) - Q1 - T1

Factor impacto CITESCORE: 26.3 - Chemistry (Q1) - Chemical Engineering (Q1)

Factor impacto SCIMAGO: 5.573 - Chemistry (miscellaneous) (Q1) - Catalysis (Q1)

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2020-113963RB-I00
Financiación: info:eu-repo/grantAgreement/ES/DGA/B29-20R
Financiación: info:eu-repo/grantAgreement/EC/H2020/859908/EU/Novel Applications in 19F Magnetic Resonance Imaging/NOVA-MRI
Financiación: info:eu-repo/grantAgreement/ES/MCIU-AEI/SAF2017-83120-C2-1-R

Tipo y forma: Article (Published version)

Área (Departamento): Área Inmunología (Dpto. Microb.Ped.Radio.Sal.Pú.)