Wyeth W Wasserman

US Patent:

60404248, Mar 21, 2000

Filed:

Jul 19, 1996

Appl. No.:

8/686617

Inventors:

William E. Fahl - Madison WI
Wyeth W. Wasserman - Madison WI

Assignee:

Wisconsin Alumni Research Foundation - Madison WI

International Classification:

C07K 14435

US Classification:

530350

Abstract:

A set of seven nuclear proteins were identified which bind to the antioxidant responsive element (ARE), a DNA sequence present in the promoters of inducible chemoprotective enzymes. One of these ARE binding proteins, here designated ARE-BP-1, has been found to exhibit binding characteristics that parallel the DNA sequences that are necessary for transcriptional induction of the chemoprotective enzymes. ARE-BP-1 is an approximately 160 kDa protein that appears to be a major control switch on the genes which act to protect cells from chemical agents. For binding by ARE-BP-1, a nucleotide sequence must include sequences outside of what was previously through to be the minimally sufficient DNA sequence for inducibility.

US Patent:

61366056, Oct 24, 2000

Filed:

Aug 26, 1994

Appl. No.:

8/297431

Inventors:

William E. Fahl - Madison WI
Andrew M. Gulick - Madison WI
T. Herbert Manoharan - Madison WI
Ralph B. Puchalski - La Jolla CA
Katharine Kramer - Madison WI
Wyeth W. Wasserman - Madison WI

Assignee:

Wisconsin Alumni Research Foundation - Madison WI

International Classification:

C12N 1500
C12N 1512
C07H 2104

US Classification:

435440

Abstract:

A method is described for the creation of novel isoforms of the enzyme glutathione S-transferase which have enhanced activity in host cells against specific toxic agents. The method includes site directed mutagenesis and selection with the targeted agent in the host cells. The sites of directed mutagenesis is the site of electrophile binding by the native form of the enzyme. This site has proven susceptible to manipulation without loss of enzymatic activity. Various techniques for enhancing the expression, activity, or localization of the expressed enzyme in mammalian cells are described. Genes for the mutant isoforms of the enzyme may be useful in cancer therapeutics to confer upon selected groups of cells heightened resistance to antineoplastic agents.