Synthesis of novel phosphonic-type activity-based probes for neutrophil serine proteases and their application in spleen lysates of different organisms

Renata Grzywa, Ewa Burchacka, Maria Łęcka, Łukasz Winiarski, Maciej Walczak, Agnieszka Łupicka-Słowik, Magdalena Wysocka, Timo Burster, Kamila Bobrek, Keri Csencsits-Smith, Adam Lesner, Marcin Sieńczyk

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2605-12
Number of pages8
JournalChemBioChem
Volume15
Issue number17
DOIs
Publication statusPublished - Nov 24 2014

Keywords

  • Humans
  • Leukocytes, Mononuclear
  • Microscopy, Fluorescence
  • Molecular Docking Simulation
  • Molecular Probes
  • Molecular Structure
  • Molecular Weight
  • Neutrophils
  • Phosphorous Acids
  • Protein Kinase Inhibitors
  • Serine Proteases
  • Spleen
  • Tissue Extracts
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Synthesis of novel phosphonic-type activity-based probes for neutrophil serine proteases and their application in spleen lysates of different organisms'. Together they form a unique fingerprint.

  • Cite this

    Grzywa, R., Burchacka, E., Łęcka, M., Winiarski, Ł., Walczak, M., Łupicka-Słowik, A., Wysocka, M., Burster, T., Bobrek, K., Csencsits-Smith, K., Lesner, A., & Sieńczyk, M. (2014). Synthesis of novel phosphonic-type activity-based probes for neutrophil serine proteases and their application in spleen lysates of different organisms. ChemBioChem, 15(17), 2605-12. https://doi.org/10.1002/cbic.201402360