Design and synthesis of acidic dipeptide hydroxamate inhibitors of procollagen C-proteinase

Annabel Ovens, John A. Joule, Karl E. Kadler

    Research output: Contribution to journalArticlepeer-review


    Procollagen C-proteinase (PCP) is essential for the cleavage of procollagen to collagen in the extracellular matrix of animals and is, therefore, of major relevance to studies of ectopic deposition of collagen during fibrosis. In this study, we describe the design and synthesis of acidic side chain hydroxamate dipeptide inhibitors of PCP having IC50 values in the range 0.1-10 μM that mimic the location of aspartic acid residues in the P1' and P2' positions (i.e. immediately C-terminal) of the PCP cleavage site in procollagen. Assays of PCP using purified human type I procollagen (a natural substrate of PCP) showed that the structure activity relationship of the inhibitors was improved with a glutamic acid mimic at the P1' position. The results also showed that the presence of an acidic side chain at the P2' position was not necessary for PCP inhibition. Marimastat and BB3103, which are highly effective inhibitors of matrix metalloproteinases and ADAMS proteinases, respectively, did not inhibit PCP. Copyright (C) 2000 European Peptide Society and John Wiley and Sons, Ltd.
    Original languageEnglish
    Pages (from-to)489-495
    Number of pages6
    JournalJournal of Peptide Science
    Issue number9
    Publication statusPublished - 2000


    • BMP-1
    • Collagen
    • Fibrosis
    • Matrix


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