Functional Proteomics on Zinc-Dependent Metalloproteinases using Inhibitor Probes
Article first published online: 12 DEC 2008
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 4, Issue 2, pages 164–170, February 13, 2009
How to Cite
Klein, T., P. Geurink, P., S. Overkleeft, H., K. Kauffman, H. and Bischoff, R. (2009), Functional Proteomics on Zinc-Dependent Metalloproteinases using Inhibitor Probes. ChemMedChem, 4: 164–170. doi: 10.1002/cmdc.200800284
- Issue published online: 4 FEB 2009
- Article first published online: 12 DEC 2008
- Manuscript Revised: 10 OCT 2008
- Manuscript Received: 29 AUG 2008
- Dutch Technology Foundation STW. Grant Number: GPC 6150
- The Netherlands Proteomics Center
- affinity probes
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.