Reagents and methods for inhibiting furin protease activity

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 5/11 (2006.01) A61K 38/07 (2006.01) A61K 38/57 (2006.01) C07K 14/81 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2327814

This invention relates to methods and reagents for inhibiting furin endoprotease activity and specifically for inhibiting furin endoprotease- mediated maturation of bioactive proteins in vivo and in vitro. The invention specifically provides peptides, peptide analogues, peptide derivatives and peptido-, organo- and chemical mimetics of said peptide inhibitors of furin endoprotease activity. Methods for using furin endoprotease inhibition to attenuate or prevent viral protein maturation, and thereby alleviate viral infections, are provided. Also provided are methods for using furin endoprotease inhibition to attenuate or prevent proteolytic processing of bacterial toxins, thereby alleviating bacterial infections methods are also provided to inhibit proteolytic processing biologically active proteins and peptides. The invention also provides pharmaceutically acceptable compositions of therapeutically effective amounts of furin endoprotease inhibitors.

La présente invention concerne des procédés et des réactifs permettant d'inhiber l'activité de l'endoprotéase furine et plus spécialement la maturation à médiation endoprotéasique de protéines bioactives in vivo et in vitro. Cette invention concerne tout spécialement des peptides analogues, des dérivés peptidiques et des peptido-, organo- et chimicomimétiques desdits inhibiteurs peptidiques de l'activité endéoprotéasique de la furine. L'invention porte également sur divers procédés d'inhibition de l'endoprotéase furine destinés à freiner ou à empêcher la maturation de protéines virales et, par là, d'atténuer les infections virales; procédés consistant à inhiber l'endoprotéase furine pour atténuer ou empêcher la transformation protéolytique des toxines bactériennes et donc d'atténuer les infections bactériennes; procédés visant à inhiber la transformation protéolythique de protéines et de peptides biologiquement actifs. La présente invention concerne enfin des compositions pharmaceutiquement actives renfermant des doses thérapeutiquement efficaces d'inhibiteurs de l'endoprotéase furine.

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