Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases
Patent
1997-10-15
1998-11-24
Hendricks, Keith D.
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Hydrolases
435196, 435199, 935 10, A61K 3846, C12N 916, C12N 922
Patent
active
058402969
ABSTRACT:
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.
REFERENCES:
patent: 5389537 (1995-02-01), Raines et al.
Alfacell Corporation, Reports and Press Releases from Oct. 1994-Nov. 1996.
Delmonte, "Novel Ribonuclease Shows Antitumor Activity in Pancreatic Cancer and Mesothelioma", Onclology Times 18 No. 6, 1996.
Kim et al., "Mechanism of Ribonuclease Cytotoxicity", J. Biol. Chem. 270 No. 52: 31097-31102, 1995.
Kim et al., "Structural Basis for the Biological Activities of Bovine Seminal Ribonuclease", J. Biol. Chem. 270, No. 18: 10525-10530, 1995.
Kobe and Deisenhofer, "A Structural Basis of the Interactions Between Leucine-Rich Repeats and Protein Ligands", Nature 374, No. 9: 183-186, 1995.
Raines et al., "Replacing a Surface Loop Endows Ribonuclease A with Angiogenic Activity", J. Biol. Chem. 270, No. 29: 17180-17184, 1995.
Schein, "From Housekeeper to Microsurgeon: The Diagnostic and Therapeutic Potential of Ribonucleases", Nature Biotechnology 15: 529-536, 1997.
Leland Peter A.
Raines Ronald T.
Schultz L. Lane
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