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Synthesis of Novel Phosphonic‐Type Activity‐Based Probes for Neutrophil Serine Proteases and Their Application in Spleen Lysates of Different Organisms
Author(s) -
Grzywa Renata,
Burchacka Ewa,
Łęcka Maria,
Winiarski Łukasz,
Walczak Maciej,
ŁupickaSłowik Agnieszka,
Wysocka Magdalena,
Burster Timo,
Bobrek Kamila,
CsencsitsSmith Keri,
Lesner Adam,
Sieńczyk Marcin
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402360
Subject(s) - proteases , serine , cathepsin g , neutrophil elastase , serine protease , elastase , biochemistry , proteinase 3 , chemistry , enzyme , innate immune system , biology , protease , inflammation , microbiology and biotechnology , immunology , receptor , myeloperoxidase
Neutrophils are a type of granulocyte important in the “first line of defense” of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low‐molecular‐weight activity‐based probes that specifically target the active sites of neutrophil proteases.