| 摘要 |
<p>Novel methods to determine matrix metalloproteinase (MMP) activity are described. In a typical embodiment of the invention, the biological fluid sample is from a patient, and the methods of the invention are useful to assess disease severity or progression, diagnose a particular disease, or develop a profile of MMP activity for inflammatory diseases such as arthritis, or cancer. A novel method of the invention involves the use of particular amino acid sequences in substrates that include but are not limited to fluorescence, colorimetric, radiometric and unlabeled substrates. A second method of the invention use neo-epitope antibodies that bind to the cleavage sites generated by collagenase 3 digestion of type IV collagen or biglycan or the peptide substrates disclosed. There is also provided a diagnostic kit for use in determining the amounts of MMP activities in biological samples comprising (a) one or more substrates with different specificities against the MMPs, (b) one or more reagents capable of inhibiting non-metalloproteinase activities, (c) one or more reagents capable of specifically inhibiting metalloproteinase activities, (d) one or more activators of metalloproteinase activities, (e) reagents capable of altering the selectivity ratios for the substrates such as gelatin or type II collagen, and (f) collagenase 3, stromelysin 1, gelatinase A, gelatinase B and/or collagenase 1 as calibration standards.</p> |
