Issue 4, 2021

Phosphinate esters as novel warheads for activity-based probes targeting serine proteases

Abstract

Activity-based protein profiling enables the specific detection of the active fraction of an enzyme and is of particular use for the profiling of proteases. The technique relies on a mechanism-based reaction between small molecule activity-based probes (ABPs) with the active enzyme. Here we report a set of new ABPs for serine proteases, specifically neutrophil serine proteases. The probes contain a phenylphosphinate warhead that mimics the P1 amino acid recognized by the primary recognition pocket of S1 family serine proteases. The warhead is easily synthesized from commercial starting materials and leads to potent probes which can be used for fluorescent in-gel protease detection and fluorescent microscopy imaging experiments.

Graphical abstract: Phosphinate esters as novel warheads for activity-based probes targeting serine proteases

Supplementary files

Article information

Article type
Paper
Submitted
21 may. 2021
Accepted
07 jul. 2021
First published
09 jul. 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 1285-1290

Phosphinate esters as novel warheads for activity-based probes targeting serine proteases

J. P. Kahler and S. H. L. Verhelst, RSC Chem. Biol., 2021, 2, 1285 DOI: 10.1039/D1CB00117E

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