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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.

SUBMITTER: Kahler JP

PROVIDER: S-EPMC8341442 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Kahler Jan Pascal JP Verhelst Steven H L SHL

RSC chemical biology 20210709 4

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 pock ...[more]

PMID: 34458842

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