Wilfried Schwab

A View on Affinity and Selectivity of Nonpeptidic Matrix Metalloproteinase Inhibitors from the Perspective of Ligands and Target

The destruction of articular cartilage is a major pathological event in Osteoarthritis (1), ultimately leading to the loss of joint function. Proteoglycan aggregates (aggrecan)are the preferred cartilage components for proteolytic attack under pathological conditions. Different cleavage sites for MMP-3 and MMP-8 have been identified at the interglobular aggrecan region. These enzymes belong to the family of matrix metalloproteinases (MMPs) — zinc endopeptidases involved in tissue remodeling and turnover of cartilage and bone. In the pathological case the degenerative potential of MMPs against components of the extracellular matrix is not longer controlled by specific tissue inhibitors. Thus MMPs are attractive targets for the treatment of arthritis and tumor progression.