Development of peptides specifically modulating the activity of KLK2 and KLK3

Hannu Koistinen, Ale Närvänen, Miikka Pakkala, Can Helim, Johanna Mattsson, Lei Zhu, Pirjo Maarit Laakkonen, Ulf-Håkan Stenman

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Abstrakti

    The prostate produces several proteases, the most abundant ones being kallikrein-related peptidase 3 (KLK3, PSA) and KLK2 (hK2), which are potential targets for tumor imaging and treatment. KLK3 expression is lower in malignant than in normal prostatic epithelium and it is further reduced in poorly differentiated tumors, in which the expression of KLK2 is increased. KLK3 has been shown to inhibit angiogenesis, whereas KLK2 may mediate tumor growth and invasion by participating in proteolytic cascades. Thus, it may be possible to control prostate cancer growth by modulating the proteolytic activity of KLK3 and KLK2. We have developed peptides that very specifically stimulate the activity of KLK3 or inhibit that of KLK2. Using these peptides we have established peptide-based methods for the determination of enzymatically active KLK3. The first-generation peptides are unstable in vivo and are rapidly cleared from the circulation. Currently we are modifying the peptides to make them suitable for in vivo applications. We have been able to considerably improve the stability of KLK2-binding peptides by cyclization. In this review we summarize the possible roles of KLK3 and KLK2 in prostate cancer and then concentrate on the development of peptides that modulate the activity of these proteases.
    Alkuperäiskielienglanti
    LehtiBiological Chemistry
    Vuosikerta389
    Numero6
    Sivut633-642
    Sivumäärä10
    ISSN1431-6730
    DOI - pysyväislinkit
    TilaJulkaistu - 2008
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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