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Trends Biochem Sci. 2018 Oct;43(10):829-844. doi: 10.1016/j.tibs.2018.07.003. Epub 2018 Aug 7.

Protease Specificity: Towards In Vivo Imaging Applications and Biomarker Discovery.

Author information

1
Jozef Stefan Institute, Department of Biochemistry and Molecular and Structural Biology, Jamova 39, SI-1000 Ljubljana, Slovenia; These authors contributed equally to this work.
2
Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland.
3
Jozef Stefan Institute, Department of Biochemistry and Molecular and Structural Biology, Jamova 39, SI-1000 Ljubljana, Slovenia.
4
NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: gsalvesen@sbpdiscovery.org.
5
Jozef Stefan Institute, Department of Biochemistry and Molecular and Structural Biology, Jamova 39, SI-1000 Ljubljana, Slovenia; Faculty of Chemistry and Chemical Technology, University of Ljubljana, Vecna pot 113, SI-1000 Ljubljana, Slovenia. Electronic address: boris.turk@ijs.si.

Abstract

Proteases are considered of major importance in biomedical research because of their crucial roles in health and disease. Their ability to hydrolyze their protein and peptide substrates at single or multiple sites, depending on their specificity, makes them unique among the enzymes. Understanding protease specificity is therefore crucial to understand their biology as well as to develop tools and drugs. Recent advancements in the fields of proteomics and chemical biology have improved our understanding of protease biology through extensive specificity profiling and identification of physiological protease substrates. There are growing efforts to transfer this knowledge into clinical modalities, but their success is often limited because of overlapping protease features, protease redundancy, and chemical tools lacking specificity. Herein, we discuss the current trends and challenges in protease research and how to exploit the growing information on protease specificities for understanding protease biology, as well as for development of selective substrates, cleavable linkers, and activity-based probes and for biomarker discovery.

KEYWORDS:

activity-based probes; biomarkers; chemical biology; focused proteomics; protease specificity; terminomics

PMID:
30097385
DOI:
10.1016/j.tibs.2018.07.003
[Indexed for MEDLINE]

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