Using Fluorogenic Peptide Substrates to Assay Matrix Metalloproteinases

Catabolism of extracellular matrix (ECM) components has been ascribed to a family of Zn^2� metalloenzymes. These matrix metalloproteinases (MMPs; also termed matrixins) are believed to be important in connective tissue remodeling during development and wound healing. MMPs have also been implicated in a variety of disease states, including arthritis, glomerulonephritis, periodontal disease, tissue ulcerations, and tumor cell invasion and metastasis (1 –4 ). Because of their potential involvement in pathological conditions, much research effort has focused on designing substrates for MMP family members. As early as 1976, Nagai and associates used synthetic collagen-sequence peptides to study the specificity of tadpole skin collagenase (5 ,6 ). Since those initial studies, a great deal of sequence specificity studies for MMP family members have been performed with peptides based on protein sequences surrounding MMP cleavage sites (7 ). Results of these studies were subsequently used to design fluorogenic substrates for the MMPs.