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Development and testing of a proof of concept Cathepsin S ProteaseTag activity-based immunoassay

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Cathepsin S (CatS) is an elastolytic cysteine protease involved in antigen presentation and is reportedly upregulated in diseases including rheumatoid arthritis (RA), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). Studies have shown increased CatS activity correlates with reduced lung function. This thesis developed highly potent and selective CatS inhibitors that were functionalised into activity-based probes (ABPs) for use in an immunoassay capable of detecting active CatS in complex patient samples. The resulting assay successfully detected CatS in sputum from CF and COPD patients, highlighting its potential for earlier diagnosis and intervention in chronic lung diseases.

Thesis is embargoed until 31 July 2031.
Date of AwardJul 2026
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsNorthern Ireland Department for the Economy
SupervisorRichard Williams (Supervisor), Timothy Ferguson (Supervisor) & Christopher Scott (Supervisor)

Keywords

  • Cathepsin S
  • imunnoassay development
  • drug discovery
  • cysteine proteases
  • Cystic Fibrosis (CF)
  • acute respiratory distress syndrome
  • inhibitors
  • activity-based probes

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