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Fluorescent diphenylphosphonate-based probes for detection of serine protease activity during inflammation.

Abstract：

:Activity-based probes are small molecules that covalently bind to the active site of a protease in an activity-dependent manner. We synthesized and characterized two fluorescent activity-based probes that target serine proteases with trypsin-like or elastase-like activity. We assessed the selectivity and potency of these probes against recombinant enzymes and demonstrated that while they are efficacious at labeling active proteases in complex protein mixtures in vitro, they are less valuable for in vivo studies. We used these probes to evaluate serine protease activity in two mouse models of acute inflammation, including pancreatitis and colitis. As anticipated, the activity of trypsin-like proteases was increased during pancreatitis. Levels of elastase-like proteases were low in pancreatic lysates and colonic luminal fluids, whether healthy or inflamed. Exogenously added recombinant neutrophil elastase was inhibited upon incubation with these samples, an effect that was augmented in inflamed samples compared to controls. These data suggest that endogenous inhibitors and elastase-degrading proteases are upregulated during inflammation.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Edgington-Mitchell LE,Barlow N,Aurelio L,Samha A,Szabo M,Graham B,Bunnett N

doi

10.1016/j.bmcl.2016.11.064

subject

Has Abstract

pub_date

2017-01-15 00:00:00

pages

254-260

issue

2

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)31218-5

journal_volume

27

pub_type

杂志文章

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