Understanding functional roles and regulation of granzyme

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Our objective is to develop selective and potent substrates and probes for human granzyme A/B. We are developing selective activity-based probes to understand the role granzymes play in the tumor microenvironment. We have begun our studies examining various cell signaling pathways and transcription factors for their role in regulating the expression, secretion, and functional activity of immune cell- and tumor-derived granzymes. To generate probes, we are using a substrate-based approach where bioisosteric replacements, constrained cyclic scaffolds, and nonpeptidic fragments are incorporated into the substrate recognition element. To further tune the reactivity, multiple serine targeting warheads are being explored.