FRET-based and other fluorescent proteinase probes

The continuous detection of enzyme activities and their application in medical diagnostics is one of the challenges in the translational sciences. Proteinases represent one of the largest groups of enzymes in the human genome and many diseases are based on malfunctions of proteolytic activity. Fluor...

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Bibliographic Details
Published in:Biotechnology journal 2014-02, Vol.9 (2), p.266-281
Main Authors: Hu, Hai-Yu, Gehrig, Stefanie, Reither, Gregor, Subramanian, Devaraj, Mall, Marcus A., Plettenburg, Oliver, Schultz, Carsten
Format: Article
Language:English
Subjects:
Activity-based probes
Animals
Caspase
Cathepsins
Cell targeting
Chronic inflammatory lung disease
Fluorescence Resonance Energy Transfer
Fluorescent Dyes
Humans
Matrix Metalloproteinases
Mice
Models, Biological
Peptide Hydrolases
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Summary:The continuous detection of enzyme activities and their application in medical diagnostics is one of the challenges in the translational sciences. Proteinases represent one of the largest groups of enzymes in the human genome and many diseases are based on malfunctions of proteolytic activity. Fluorescent sensors may shed light on regular and irregular proteinase activity in vitro and in vivo and provide a deeper insight into the function of these enzymes and their role in pathophysiological processes. The focus of this review is on Förster resonance energy transfer (FRET)‐based proteinase sensors and reporters because these probes are most likely to provide quantitative data. The medical relevance of proteinases are discussed using lung diseases as a prominent example. Probe design and probe targeting are described and fluorescent probe development for disease‐relevant proteinases, including matrix‐metalloproteinases, cathepsins, caspases, and other selected proteinases, is reviewed. Fluorescent probes, in particular ratiometric FRET (Förster resonance energy transfer) probes, made it possible to observe enzyme activities in intact cells and living organisms. In this review, the authors summarize the various types of proteinase‐sensitive fluorescent FRET probes as well as their applications. In the future, these probes will help determine disease states of patients and evaluate therapeutic effects of drugs and drug candidates.
ISSN:1860-6768
1860-7314
DOI:10.1002/biot.201300201