NIH Research Festival
–
–
Granzymes are a family of serine proteases found in the secretory granules of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) as essential components of the immune response against infected or cancerous cells. Despite being the most abundant of the five human granzymes (A, B, H, K, and M), relatively little is known about the role that granzyme A (GzmA) plays in the tumor immune microenvironment, partly due to a lack of convenient tools that can measure active GzmA with spatiotemporal control. To this end, we have designed and synthesized activity-based probes (ABPs) that leverage the catalytic activity of GzmA to generate a fluorescent signal. Our probes utilize a tetrapeptide substrate sequence as a recognition motif and harness a serine-reactive phosphinate warhead to form covalent conjugation in the active site. We demonstrate that these probes are highly efficient and selective for detecting GzmA activity in NK cells with the potential as imaging tools to study GzmA biology in functional immune cells within the tumor microenvironment.
Scientific Focus Area: Chemical Biology
This page was last updated on Tuesday, August 6, 2024