Abstract: A method is provided of decreasing or increasing the activity of a Pappalysin polypeptide by decreasing or increasing the level of interacting Pappalysin and stanniocalcin polypeptides. A method is also provided of preventing, treating or ameliorating a clinical condition in a mammalian subject, such as a human being, said method comprising administering to said mammalian subject, such as human being an effective amount of a stanniocalcin polypeptide. Moreover, a method is provided of preventing, treating or ameliorating a clinical condition in a mammalian subject, such as a human being, said method comprising administering to said mammalian subject, such as human being an effective amount of an agent capable of antagonizing interaction of a stanniocalcin polypeptide with a Pappalysin polypeptide.

Abstract: A method is provided of decreasing or increasing the activity of a Pappalysin polypeptide by decreasing or increasing the level of interacting Pappalysin and stanniocalcin polypeptides. A method is also provided of preventing, treating or ameliorating a clinical condition in a mammalian subject, such as a human being, said method comprising administering to said mammalian subject, such as human being an effective amount of a stanniocalcin polypeptide. Moreover, a method is provided of preventing, treating or ameliorating a clinical condition in a mammalian subject, such as a human being, said method comprising administering to said mammalian subject, such as human being an effective amount of an agent capable of antagonizing interaction of a stanniocalcin polypeptide with a Pappalysin polypeptide.

Abstract: A method is provided of decreasing or increasing the activity of a Pappalysin polypeptide by decreasing or increasing the level of interacting Pappalysin and stanniocalcin polypeptides. A method is also provided of preventing, treating or ameliorating a clinical condition in a mammalian subject, such as a human being, said method comprising administering to said mammalian subject, such as human being an effective amount of a stanniocalcin polypeptide. Moreover, a method is provided of preventing, treating or ameliorating a clinical condition in a mammalian subject, such as a human being, said method comprising administering to said mammalian subject, such as human being an effective amount of an agent capable of antagonizing interaction of a stanniocalcin polypeptide with a Pappalysin polypeptide.

Abstract: The present invention relates in one embodiment to PAPP-A exosite(s) interactors such as antibodies which bind to a region comprising LNR3 of PAPP-A and efficiently inhibit proteolysis of IGFBP-4, but not -5. The region comprising LNR3 represents a substrate binding exosite, which can be targeted for selective proteolytic inhibition. Accordingly, the present invention relates in one embodiment to differential inhibition of natural protease substrates by exosite targeting.

Abstract: The present invention relates in one embodiment to PAPP-A exosite(s) interactors such as antibodies which bind to a region comprising LNR3 of PAPP-A and efficiently inhibit proteolysis of IGFBP-4, but not -5. The region comprising LNR3 represents a substrate binding exosite, which can be targeted for selective proteolytic inhibition. Accordingly, the present invention relates in one embodiment to differential inhibition of natural protease substrates by exosite targeting.