Glutathione s-transferase

Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Transferases

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424529, 435193, 536 232, 536 235, A61K 3845, C12N 910

Patent

active

059765283

ABSTRACT:
The present invention provides a human glutathione S-transferase (HGST) and polynucleotides which identify and encode HGST. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding HGST and a method for producing HGST. The invention also provides for agonists, antibodies, or antagonists specifically binding HGST, and their use, in the prevention and treatment of cancer and other diseases associated with the expression of HGST. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding HGST for the treatment of cancer and other diseases associated with the expression of HGST. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, and antibodies specifically binding HGST.

REFERENCES:
Lee, HC et al., "A molecular genetic approach for the identification of essential residues in human glutathione S-transferase function in Escherichia coli" J. Biol. Chem. 270(1):99-109 (1995).
Stenberg, G et al., "Effects of directed mutagenesis on conserved arginine residues in a human Class Alpha glutathione transferase" Biochem. J. 274:549-555 (1991).
Thier, R et al., "Expression of mammalian glutathione S-transferase 5-5 in Salmonella typhimurium TA1535 leads to base-pair mutations upon exposure to dihalomethanes" Proc. Natl. Acad. Sci. USA 90:8567-8580 (1993).
Simula, TP et al., Human glutathione S-transferase-expressing Salmonella typhimurium tester strains to study the activation/detoxification of mutagenic compounds: studies with halogenated compounds, aromatic amines and aflatoxin B.sub.1 Carcinogenesis 14(7):1371-1376 (1993).
Dirven, HAAM et al., "Involvement of Human Glutathione S-Transferase Isoenzymes in the Conjugation of Cyclophosphamide Metabolites with Glutathione" Cancer Res. 54:6215-6220 (1994).
Klone, A et al., "Cloning, sequencing and characterization of the human Alpha glutathione S-transferase gene corresponding to the cDNA clone pGTH2" Biochem. J. 285:925-928 (1992) (Accession GI 825605).
Stenberg, G et al., "Heterologous expression of recombinant human glutathione transferase A1-1 from a hepatoma cell line" Protein Expr Purif 3:80-84 (1992) (Accession GI 259141).
Zimniak, P et al., "A subgroup of class .varies. glutathione S-transferases Cloning of cDNA for mouse lung glutathione S-transferase GST 5.7" FEBS Lett 313 (2):173-176 (1992) (Accession GI 193710).
Database: EMBL Sequences, EMBL, Heidelberg, FRG Accession No. H27975, Jul. 18, 1995, Hillier L. Et al., "H.sapiens cDNA clone 162882 similar to mouse glutathione S-transferase GST5.7", XP002057353.
Database: EMBL Sequences, EMBL, Heidelberg, FRG Accession No. WO5487, May 8, 1996, Hillier, L., et al., "Soares fetal lung NbHL19W H. sapiens cDNA clone 299299 similar to human glutathione S-transferase A2-2," XP002057354.
Database: EMBL Sequences, EMBL, Heidelberg, FRG Accession No. W76501, Jun. 23, 1996, Hillier, L., et al., Soares fetal heart NbHH19W, H. sapiens cDNA clone 345309 similar to mouse glutathione S-transferase GST5.7, XP002057355.

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