Detection of Active Granzyme A in NK92 Cells with Fluorescent Activity-Based Probe

J Med Chem. 2020 Mar 26;63(6):3359-3369. doi: 10.1021/acs.jmedchem.9b02042. Epub 2020 Mar 16.


Cytotoxic T-lymphocytes (CTLs) and natural killer cells (NKs) kill compromised cells to defend against tumor and viral infections. Both effector cell types use multiple strategies to induce target cell death including Fas/CD95 activation and the release of perforin and a group of lymphocyte granule serine proteases called granzymes. Granzymes have relatively broad and overlapping substrate specificities and may hydrolyze a wide range of peptidic epitopes; it is therefore challenging to identify their natural and synthetic substrates and to distinguish their localization and functions. Here, we present a specific and potent substrate, an inhibitor, and an activity-based probe of Granzyme A (GrA) that can be used to follow functional GrA in cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Coumarins / chemical synthesis
  • Coumarins / pharmacology*
  • Coumarins / toxicity
  • Drug Design
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / pharmacology*
  • Fluorescent Dyes / toxicity
  • Granzymes / analysis*
  • Granzymes / chemistry
  • Humans
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacology*
  • Oligopeptides / toxicity
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / pharmacology*
  • Serine Proteinase Inhibitors / toxicity
  • Substrate Specificity


  • Coumarins
  • Fluorescent Dyes
  • Oligopeptides
  • Serine Proteinase Inhibitors
  • Granzymes
  • GZMA protein, human