Functional Proteomics on Zinc-Dependent Metalloproteinases using Inhibitor Probes

• Published in: ChemMedChem 2009-02, Vol.4 (2), p.164-170
• Main Authors: Klein, Theo, P. Geurink, Paul, S. Overkleeft, Hermen, K. Kauffman, Henk, Bischoff, Rainer
• Format: Article
• Language: English
• Subjects: affinity probes; Hydrolysis; inhibitors; metalloenzymes; Metalloproteases - antagonists & inhibitors; Metalloproteases - metabolism; metzincins; Molecular Probes; Protease Inhibitors - pharmacology; Proteomics; Zinc - metabolism
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.200800284

Zinc‐dependent metalloproteinases such as matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs) are potential therapeutic targets in many diseases. To better understand their complex role in health and disease, new methodology for activity determination is under development. This concept gives an overview of the available methods for activity‐based proteomic research on these enzymes. Metzincins are a family of zinc(II)‐dependent metalloproteinases with well known members such as the matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs). Metzincins are largely responsible for the modulation and regulation of the extracellular matrix by proteolytic degradation of extracellular matrix (ECM) proteins, and by liberation or production of biologically active proteins from their pro‐forms. Since metzincin activity is strictly regulated in vivo, novel analysis methods are necessary to elucidate the role of the active enzymes in health and disease. This concept gives an overview of available methods, and describes an approach to use synthetic metzincin inhibitors as affinity probes for selective determination of active metzincins in biological and clinical samples. Zinc‐dependent metalloproteinases such as matrix metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs) are potential therapeutic targets in many diseases. To better understand their complex role in health and disease, new methodology for activity determination is under development. This concept gives an overview of the available methods for activity‐based proteomic research on these enzymes.