Functional proteomics on zinc-dependent metalloproteinases using inhibitor probes.

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.