Human ribonuclease a with reduced ribonuclease inhibitor...

C - Chemistry – Metallurgy – 12 – N

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Details

C12N 15/55 (2006.01) A61K 38/46 (2006.01) C12N 9/22 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2306442

Modified ribonucleases belonging to the RNase A superfamily of ribonucleases is disclosed. Each modified ribonuclease has a mutation in the loop region corresponding to amino acids 85-94 of bovine pancreatic RNase A. Each modified ribonuclease has reduced binding affinity for ribonuclease inhibitor (RI), wild-type ribonuclease activity, and exhibits enhanced cytotoxicity toward tumor cells, relative to the wild-type ribonuclease. Also disclosed is a method for obtaining a modified ribonuclease having reduced binding affinity for RI, wild-type ribonuclease activity, and enhanced cytotoxicity.

L'invention concerne des ribonucléases modifiées faisant partie des RNases A de la superfamille des ribonucléases. Chaque ribonucléase modifiée présente une mutation dans la région de la boucle correspondant aux acides aminés 85-94 de la RNase A pancréatique bovine. Elle possède 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. L'invention concerne également une méthode permettant d'obtenir une ribonucléase modifiée qui possède une affinité réduite pour RI, une activité ribonucléase de type sauvage et une cytotoxicité accrue.

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