Noninvasive optical detection of granzyme B from natural killer cells with enzyme-activated fluorogenic probes.

ABSTRACT: Natural killer (NK) cells are key innate immunity effectors that combat viral infections and control several cancer types. For their immune function, human NK cells rely largely on five different cytotoxic proteases, called granzymes (A/B/H/K/M). Granzyme B (GrB) initiates at least three distinct cell death pathways, but key aspects of its function remain unexplored because selective probes that detect its activity are currently lacking. In this study, we used a set of unnatural amino acids to fully map the substrate preferences of GrB, demonstrating previously unknown GrB substrate preferences. We then used these preferences to design substrate-based inhibitors and a GrB-activatable activity-based fluorogenic probe. We show that our GrB probes do not significantly react with caspases, mak

SUBMITTER: Janiszewski T 

PROVIDER: S-EPMC7363135 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature