Selective exosite inhibition of papp-a activity against igfbp-4

Details Selective exosite inhibition of papp-a activity against igfbp-4 Selective exosite inhibition of papp-a activity against igfbp-4

C - Chemistry, Metallurgy

07

K

C07K 14/435 (2006.01) A61K 38/17 (2006.01) C07K 14/47 (2006.01) C07K 16/18 (2006.01) C07K 16/40 (2006.01) C12N 9/64 (2006.01)

Patent

CA 2713055

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 inven-tion relates in one embodiment to differential inhibition of natural protease substrates by exosite targeting.

La présente invention porte, dans un mode de réalisation, sur des agents interagissant avec le ou les exosites de PAPP-A tels que des anticorps qui se lient à une région comprenant LNR3 de PAPP-A et inhibent efficacement la protéolyse de IGFBP-4, mais pas de -5. La région comprenant LNR3 représente un exosite de liaison à un substrat, qui peut être ciblé pour une inhibition protéolytique sélective. En conséquence, la présente invention porte, dans un mode de réalisation, sur une inhibition différentielle de substrats de protéases naturelles par ciblage d'exosites.

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