Activity based probes for proteases: applications to biomarker discovery, molecular imaging and drug screening.
Recent advances in global genomic and proteomic methods have lead to a greater understanding of how genes and proteins function in complex networks within a cell. One of the major limitations in these methodologies is their inability to provide information on the dynamic, post-translational regulation of enzymatic proteins. In particular proteases are often synthesized as inactive zymogens that need to be activated in order to carry out specific biological processes. Thus, methods that allow direct monitoring of protease activity in the context of a living cell or whole animal will be required to begin to understand the systems-wide functional roles of proteases. In this review, we discuss the development and applications of activity based probes (ABPs) to study proteases and their role in pathological processes. Specifically we focus on application of this technique for biomarker discovery, in vivo imaging and drug screening.
Fonović
Marko
M
Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Bogyo
Matthew
M
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D020134:Catalytic Domain; D020650:Combinatorial Chemistry Techniques; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015195:Drug Design; D004789:Enzyme Activation; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D015335:Molecular Probes; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D040081:Protein Array Analysis; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D012697:Serine Endopeptidases / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods
D015415:Biomarkers; D005456:Fluorescent Dyes; D015335:Molecular Probes; D011480:Protease Inhibitors; D045726:Metalloproteases; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases