Engineered cytotoxic ribonclease
AssigneeWisconsin Alumni Research Foundation
InventorRonald T. Raines
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Abstract
Modified ribonucleases belonging to the RNase A superfamily of ribonucleases is 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.
Claims10
An engineered cytotoxic ribonuclease comprising an amino acid sequence for a ribonuclease of the RNase A superfamily and a steric hindrance moiety covalently attached to an amino acid in the ribonuclease in a loop region functionally equivalent to the region of amino acid residues 85-94 of bovine pancreatic RNase A, the engineered ribonuclease having reduced binding affinity for ribonuclease inhibitor due to steric hindrance by the steric hindrance moiety, the modified ribonuclease retaining ribonucleolytic activity.
A modified ribonuclease of the RNase A superfamily, the modified ribonuclease engineered by human modification thereof, the modified ribonuclease A having an alteration to its structure as compared to the corresponding wild-type ribonuclease, the alteration being the addition to the protein of a steric hindrance moiety, the steric hindrance moiety being covalently attached to an amino acid corresponding in position to amino acids 85-94 of RNase A, the steric hindrance moiety being sufficient in size to hinder binding to ribonuclease inhibitor while not interfering with ribonucleolytic activity.
Dependencies are inferred from the claim text.