title: Activity-based probes for the study of proteases: recent advances and developments.
abstract: Proteases are important targets for the treatment of human disease. Several protease inhibitors have failed in clinical trials due to a lack of in vivo specificity, indicating the need for studies of protease function and inhibition in complex, disease-related models. The tight post-translational regulation of protease activity complicates protease analysis by traditional proteomics methods. Activity-based protein profiling is a powerful technique that can resolve this issue. It uses small-molecule tools-activity-based probes-to label and analyze active enzymes in lysates, cells, and whole animals. Over the last twelve years, a wide variety of protease activity-based probes have been developed. These synthetic efforts have enabled techniques ranging from real-time in vivo imaging of protease activity to high-throughput screening of uncharacterized proteases. This Review introduces the general principles of activity-based protein profiling and describes the recent advancements in probe design and analysis techniques, which have increased the knowledge of protease biology and will aid future protease drug discovery.
authors.affiliation: Center for Integrated Protein Science Munich (CIPS(M)), Lehrstuhl für Chemie der Biopolymere, Technische Universität München, Weihenstephaner Berg 3, 85354 Freising, Germany.
authors.forename: Sevnur
authors.initials: S
authors.lastname: Serim
authors.forename: Ute
authors.initials: U
authors.lastname: Haedke
authors.forename: Steven H L
authors.initials: SH
authors.lastname: Verhelst
mesh_terms: D000818:Animals; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D006801:Humans; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics
chemical_list: D005456:Fluorescent Dyes; D015335:Molecular Probes; D010447:Peptide Hydrolases