title: Strategies for detection and quantification of cysteine cathepsins-evolution from bench to bedside.
abstract: The cysteine cathepsins are a family of closely related thiol proteases, normally found in the endosomal and lysosomal compartments of cells. A growing body of evidence has clearly linked the dysregulated activity of these proteases with many diseases and pathological conditions, offering therapeutic, prognostic and diagnostic potential. However, these proteases are synthesised as inactive precursors and once activated, are controlled by factors such as pH and presence of endogenous inhibitors, meaning that overall protein and activity levels do not necessarily correlate. In order to fully appreciate the role and potential of these proteases, tools are required that can detect and quantify overall cathepsin activity. Two main strategies have evolved; synthetic substrates and protease-labelling with affinity-binding probes (or activity-based probes). This review examines recent innovations in these approaches as the field moves towards developing tools that could ultimately be used in patients for diagnostic or prognostic applications.
authors.affiliation: Molecular Therapeutics, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Hughes
authors.affiliation: Molecular Therapeutics, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors.forename: Roberta E
authors.initials: RE
authors.lastname: Burden
authors.affiliation: Molecular Therapeutics, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Gilmore
authors.affiliation: Molecular Therapeutics, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK. Electronic address: c.scott@qub.ac.uk.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Scott
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D057075:Enzyme Assays / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000201:enzymology; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D013379:Substrate Specificity; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D002403:Cathepsins; D003545:Cysteine
keywords: Activity-based probe; Affinity binding probe; Cathepsin; Cysteine proteinase; Proteolysis; Quenched substrate