Development of Granzyme A Turn-ON Fluorescent Activity-Based Probes.

ABSTRACT: Granzyme A (GzmA), a serine protease highly expressed in cytotoxic immune cells, plays complex roles in antitumor immunity and inflammation. While elevated GzmA levels correlate with favorable outcomes in certain cancers, extracellular GzmA has been implicated in promoting tumorigenesis via inflammatory pathways. These contrasting functions highlight the need for selective tools that can detect GzmA activity with high spatiotemporal resolution in native biological contexts. A series of quenched activity-based probes that fluoresce only upon covalent binding to active GzmA have been developed. The lead probe, featuring the Ile-Gly-Asn-Arg recognition sequence, a phenyl phosphinate ester warhead, and a near-infrared sulfo-Cy5/QSY21 fluorophore/quencher pair, exhibits high reactivity, selecti

SUBMITTER: Malespini SM 

PROVIDER: S-EPMC12703428 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature