Abstract
Prostromelysin, a member of the family of matrix metalloproteinases, is secreted as a zymogen which is activated after cleavage of the His81−Phe82 bond. The 82 amino acid propeptide that is removed during activation contains 12 amino acids, MRKPRC75GVPDVG, that are highly conserved in all MMPs. We evaluated a series of peptides that span this region for their ability to inhibit stromelysin. The hexapeptide, Ac-RCGVPD, and the pentapeptide, Ac-RCGVP had IC50 values of approx. 10 μM. The tetrapeptide, Ac-RCGV, was somewhat less potent with an IC50 of 60 μM. Smaller peptides, e. g. Ac-RCG, were significantly less potent as inhibitors. Substitutions of Cys75 with Ser resulted in a complete loss of inhibitory activity. The peptides in this series also inhibited human fibroblast collagenase.
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Hanglow, A.C., Lugo, A., Walsky, R. et al. Peptides based on the conserved prodomain sequence of matrix metalloproteinases inhibit human stromelysin and collagenase. Agents and Actions 39 (Suppl 1), C148–C150 (1993). https://doi.org/10.1007/BF01972749
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DOI: https://doi.org/10.1007/BF01972749