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Recent Advances in Activity-Based Protein Profiling of Proteases

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Book cover Activity-Based Protein Profiling

Abstract

The activity of proteases is tightly regulated, and dysregulation is linked to a variety of human diseases. For this reason, ABPP is a well-suited method to study protease biology and the design of protease probes has pushed the boundaries of ABPP. The development of highly selective protease probes is still a challenging task. After an introduction, the first section of this chapter discusses several strategies to enable detection of a single active protease species. These range from the usage of non-natural amino acids, combination of probes with antibodies, and engineering of the target proteases. A next section describes the different types of detection tags that facilitate the read-out possibilities including various types of imaging methods and mass spectrometry-based target identification. The power of protease ABPP is illustrated by examples for a selected number of proteases. It is expected that some protease probes that have been evaluated in animal models of human disease will find translation into clinical application in the near future.

Suravi Chakrabarty, Jan Pascal Kahler, Merel A. T. van de Plassche, Roeland Vanhoutte—equal contribution

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Acknowledgements

The work in the Verhelst Laboratory is generously supported by the FWO, Stichting Alzheimer Onderzoek, KU Leuven, the Deutsche Forschungsgemeinschaft (DFG), the Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen, the Senatsverwaltung für Technologie und Forschung des Landes Berlin, and the Bundesministerium für Bildung und Forschung.

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Correspondence to Steven H. L. Verhelst .

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Chakrabarty, S., Kahler, J.P., van de Plassche, M.A.T., Vanhoutte, R., Verhelst, S.H.L. (2018). Recent Advances in Activity-Based Protein Profiling of Proteases. In: Cravatt, B., Hsu, KL., Weerapana, E. (eds) Activity-Based Protein Profiling. Current Topics in Microbiology and Immunology, vol 420. Springer, Cham. https://doi.org/10.1007/82_2018_138

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