Imaging of proteases using activity-based probes

Abstract

Proteases (proteolytic enzymes) are proteins that catalyze one of the most important biochemical reactions, namely the hydrolysis of the peptide bond in peptide and protein substrates. Therefore these molecular biocatalysts participate in virtually all living processes. The proper balance between intact and processed protease substrates enables to maintenance of homeostasis from a single-cell level to the whole living system. However, when the proteolytic activity is altered, this delicate balance is disturbed, which might lead to the development of a plethora of diseases. Given this, monitoring proteolytic activity is indispensable to understanding how proteases operate in disease lesions and how their altered catalytic activity might be harnessed for a better diagnosis and treatment. In this manuscript, we provide a critical review of the recent development of protease chemical probes which are small molecules that detect proteolytic activity by interacting with protease active site, individual proteases as well as complex proteolytic networks.