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

Journal of Medicinal Chemistry
Sonia KołtPaulina Kasperkiewicz

Abstract

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.

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Citations

Apr 28, 2021·Journal of Medicinal Chemistry·Hong-Rae KimEuna Yoo
May 18, 2021·Frontiers in Chemistry·Paulina Kasperkiewicz

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Methods Mentioned

BETA
gene knockout
phage display

Software Mentioned

GrA
Excel
GraphPad Prism
SoftMax
HyCoSuL

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