Marimastat caproKit™ for functional isolation of matrix metalloproteinases
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. MMPs play an important role in tissue remodeling which is associated with several patho- and physiological processes such as tissue repair, angiogenesis, morphogenesis, arthritis, and metastasis. MMPs are secreted as proenzymes and require extracellular activation. Under physiological conditions the activity of MMPs is regulated at the transcriptional as well as the posttranslational level. The transcription is mediated via MAP-kinases or via serine/threonine-kinases and initiated via the transcription factor AP-1 and Ets. The mechanisms are complex and not fully understood (1, 2). MMPs have first been described in vertebrates, but have since been identified in invertebrates and plants.
Members of the MMP family share a common structure consisting of a pro-peptide which needs to be removed to activate the enzyme, and a catalytic domain with an active site that contains the Zn2+ ion bound by three histidine resiudes. The third structural element is a haemopexin-like C-terminal domain. With its four bladed ß-propeller structure it is important for determining the substrate specificity and to mediate the interaction with specific tissue inhibitors of metalloproteases (TIMPs). These two domains are linked by a hinge region. The specific TIMPs are homologous proteins of 21 - 29 kDa in size and consist of two domains, an N-terminal inhibitory domain and a C-terminal binding/mediation domain.
Synthetic inhibitors which generally contain a chelating group for the binding of the catalytic Zn2+ ion at the MMP active site are particularly potent inhibitors. Unspecific inhibitors interact with various binding pockets on the MMP of interest. One of the potent broadband MMP inhibitors is marimastat, a synthetic hydroxamate with potent antineoplastic activity (3, 4). Marimastat chelates the Zn2+ ion in the active site of many MMPs.
Because of its broadband inhibitory and binding properties, marimastat is an ideal selectivity function for a MMP-specific Capture Compound™ to investigate MMPs for example in biomarker discovery studies (5).
