Engineered cytotoxic ribonuclease

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 9/22 (2006.01)

Patent

CA 2351735

Modified ribonucleases belonging to the RNase A superfamily of ribonucleases are disclosed. Each modified ribonuclease has a steric hindrance moiety added to it in the loop region corresponding to amino acids 85-94 of bovine pancreatic RNase A. Such a modified ribonuclease has reduced binding affinity for ribonuclease inhibitor (RI), exhibits wild-type ribonuclease activity, and exhibits enhanced cytotoxicity toward tumor cells, relative to the wild-type ribonuclease.

L'invention concerne des ribonucléases modifiées appartenant à la superfamille des Rnases A. Sur chaque ribonucléase modifiée, une fraction à encombrement stérique est ajoutée dans la région de boucle correspondant aux acides aminés 85-94 de la RNase A pancréatique bovine. Lesdites ribonucléases modifiées possèdent une affinité de liaison réduite pour l'inhibiteur de la ribonucléase (RI), une activité ribonucléase de type sauvage et, par rapport à la ribonucléase de type sauvage, une plus grande cytotoxicité pour les cellules tumorales.

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