title: Synthesis of novel phosphonic-type activity-based probes for neutrophil serine proteases and their application in spleen lysates of different organisms.
abstract: 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.
authors.affiliation: Division Of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wroclaw (Poland).
authors.forename: Renata
authors.initials: R
authors.lastname: Grzywa
authors.forename: Ewa
authors.initials: E
authors.lastname: Burchacka
authors.forename: Maria
authors.initials: M
authors.lastname: Łęcka
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Winiarski
authors.forename: Maciej
authors.initials: M
authors.lastname: Walczak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Łupicka-Słowik
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wysocka
authors.forename: Timo
authors.initials: T
authors.lastname: Burster
authors.forename: Kamila
authors.initials: K
authors.lastname: Bobrek
authors.forename: Keri
authors.initials: K
authors.lastname: Csencsits-Smith
authors.forename: Adam
authors.initials: A
authors.lastname: Lesner
authors.forename: Marcin
authors.initials: M
authors.lastname: Sieńczyk
mesh_terms: D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology; D008856:Microscopy, Fluorescence; D062105:Molecular Docking Simulation; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D008970:Molecular Weight; D009504:Neutrophils / Q000201:enzymology*; D010757:Phosphorous Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057057:Serine Proteases / Q000378:metabolism*; D013154:Spleen / Q000737:chemistry* / Q000201:enzymology; D014020:Tissue Extracts
chemical_list: D015335:Molecular Probes; D010757:Phosphorous Acids; D047428:Protein Kinase Inhibitors; D014020:Tissue Extracts; C570063:phosphonic acid; D057057:Serine Proteases
keywords: activity-based probes; aminophosphonates; inhibitors; neutrophil serine proteases; peptidomimetics