Chemistry: molecular biology and microbiology – Treatment of micro-organisms or enzymes with electrical or... – Modification of viruses
Patent
1995-05-04
1999-03-09
Ketter, James
Chemistry: molecular biology and microbiology
Treatment of micro-organisms or enzymes with electrical or...
Modification of viruses
532502, C12N 1500, C07J 100
Patent
active
058799176
ABSTRACT:
The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.
REFERENCES:
patent: 3299104 (1967-01-01), Fex et al.
patent: 5354745 (1994-10-01), Tamura et al.
Nobori et al. (1994), Deletions of the Cyclin-Dependent Kinase-4 Inhibitor Gene in Multiple Human Cancers,: 368 Nature 753-756.
Xiong et al. (1993), "Subunit Rearrangement of the Cyclin-Dependent Kinases is Associated with Cellular Transformation," 7 Genes & Dev., 1572-1583.
Keyomarsi et al. (1993), "Redundant Cyclin Overexpression and Gene Amplification in Breast Cancer Cells," 90 Proc. Nat'l. Acad. Sci., USA 1112-1116.
Stephen et al. (1992), "Mutant Conformation of p53," 225 J. Mol. Biol. 577-583.
Hollstein et al. (1991), "p53 Mutations in Human Cancers," 253 Science 49-53.
Marx (1990), "Genetic Defect Identified in Rare Cancer Syndrome," 250 Science 1209.
Malkin et al. (1990), "Germ Line p53 Mutations in a Familial Syndrome of Breast Cancer, Sarcomas, and Other Neoplasms," 250 Science 1233-1238.
Vogelstein (1990), "A Deadly Inheritance," 348 Nature 681-682.
Srivastava et al. (1990), "Germ-Line Transmission of a Mutated p53 Gene in a Cancer-prone Family with Li-Fraumeni Syndrome," 348 Nature 747-749.
Gannon et al. (1990), "Activating Mutations in p53 Produce a Common Conformational Effect. A Monoclonal Antibody Specific For The Mutant Form," 9 EMBO J. 5:1595-1602.
Muntzing et al. (1972), "Lipofuscin in Malignant and Non-Malignant Human Prostatic Tissue," 77 Z. Krebsforsch 166-170.
Niculescu-Duvaz et al. (1966), "Potential Anticancer Agents II Urethan Type Nitrogen Mustards of Some Natural Sex Hormones," 10 J. Med. Chem. 172-174.
Holley et al. (1992), "Targeting of Tumor Cells and DNA by a Chlorambucil-Spermidine Conjugate," 52 Cancer Res. 4190-4195.
Kosano et al. (1992), "Growth-Inhibitory Action of An Estrogen-Chloramucil Conjugate (KM2210) in Human Breast Cancer Cell Line MCF-7: Its Relationship to Reduction of Estrogen Receptor and Transforming Growth Factor-a Section," 52 Cancer Res. 1187-1191.
Otto et al. (1991), "Dissociation of Estrogenic and Cytotoxic Properties of an Estrogen Receptor-Binding Platinum Complex in Human Breast Cancer Cell Lines," 51 Cancer Res. 3217-3223. pyridine! dichloroplatinum(II): Complexes With A Selective Action on Estrogen Receptor Positive Mammary Tumors," 34 J. Med. Chem. 7:2145-2152.
von Angerer et al. (1984), "2Phenylindoles -- Relationship Between Structure, Estrogen Receptor Affinity, and Mammary Tumor Inhibiting Activity in the Rat," 27 J. Med. Chem. 1439-1447.
Georgiadis et al. (1987), "Synthesis and Biological Studies Steroidal cis-Platinum(II) Complexes," 138 Inorg. Chim. Acta 249-252.
Wakeling and Bowler (1988), "Novel Antioestrogens Without Partial Agonist Activity," 31 J. Steroid Biochem. No. 4B:654-653.
Jones et al. (1984) "Antiestrogens 2. Structure-Activity Studies in a oxy!-phenyl!methanone Hydrochloride (LY156768), a Remarkably Effective Estrogen Antagonist With Only Minimal Intrinsic Estrogenicity," 27 J. Med. Chem. 1057-1066.
Leclercq et al. (1983), "Guide-Lines in the Design of New Antiestrogens and Cytotoxic-Linked Estrogens For The Treatment of Breast Cancer," 19 J. Steroid Biochem. 75-85.
Katzenellenbogen et al. (1980), "The Chemistry of Estrogens and Antiestrogens: Relationships Between Structure, Receptor Binding, and Biological Activity," Estrogens in the Environment (Mclachlan, ed.) 33-51.
Jordan et al. (1980), "Structural Derivatives of Tamifoxen and Oestradiol 3-methyl Ether as Potential Alkylating Antioestrogens," 17 Eur. J. Cancer 193-201.
Redeuilh et al. (1980), "Properties of Biospecific Absorbents Obtained by Immobilization of Oestradiol 7a Deriviatives, For Purification of Calf-Uterine Cytosol Oestradiol Receptor," 106 Eur. J. Biochem. 481-493.
Jones et al. (1993), "Preferential Binding of the Xeroderma Pigmentosum Group A Complementing Protein to Damaged DNA," 32 Biochem. 12096-12104.
Batist et al. (1989), "Enhanced DNA Cross-Link Removal: The Apparent Mechanism of Resistance in a Clinically Relevant Melphalan-Resistant Human Breast Cancer Cell Line," 36 Mol. Pharmacol. 224-230.
Devchand et al. (1993), "Uracil-DNA Glycosylase As A Probe For Protein-DNA Interactions," 21 Nucl. Acids Res. 15:3437-3443.
Sibghat-Ullah and Sancar (1990), "Substrate Overlap and Functional Competition Between Human Nucleotide Excision Repair and Escherichia coli Photolyase and (A)BC Excision Nuclease," 29 Biochem. 5711-5718.
Lippard (1994), "Structural and Biological Consequences of Platinum Anticancer Drug Binding to DNA," Chapter 4 of Proceedings of the Robert A. Welch Foundation 37th Conference on Chemical Research, 40 Years of the DNA Double Helix, Oct. 25-26, 1993, The Westin Oaks Hotel, Houston, Texas (1994).
Bruhn et al. (1993), "Isolation and Characterization of cDNA Clones Encoding the Drosophila Homolog of the HMG-Box SSRP Family That Recognized Specific DNA Structures," 21 Nucl. Acids Res. 1643-1646.
Bradley et al. (1993), "Mutagenicity and Genotoxicity of the Major DNA Adduct of the Anti-Tumor Druge cis-Diamminedichloroplatinum(II)," 32 Biochem. 982-988.
Brown et al. (1993), "Ixr1, a Yeast Protein That Binds to Platinated DNA and Confers Sensitivity to Cisplatin," 261 Science 603-605.
Weir et al. (1993), "Structure of the HMG Box Motif in the B-Domain of HMG1," 12 EMBO J. 4:1311-1319.
Pil et al. (1993), "High-Mobility Group 1 Protein Mediates DNA Bending as Determined by Ring Closures," 90 Proc. Nat'l. Acad. Sci. USA 9465-9469.
Dabholkar et al. (1992), "Determinants of Cisplatin Sensitivity in Non-Malignant Non-Drug Selected Human T Cells," 274 Mut. Res. 45-56.
Treiber et al. (1992), "An Ultraviolet Light-Damaged DNA Recognition Protein Absent in Xeroderma Pigmentosum Group E Cells Binds Selectively to Pyrimidine (6-4) Pyrimidome Photoproducts," 20 Nucl. Acids Res. 21:5805-5810.
Szymkowski et al. (1992), "An Intrastrand d(GpG) Platinum Crosslink in Duplex M13 DNA is Refractory to Repair by Human Cell Extracts," 89 Proc. Nat'l. Acad. Sci. USA 10772-10776.
Zhen et al. (1992), "Increased Gene-Specific Repair of Cisplatin Interstrand Cross-Links in Cisplatin-Resistant Human Ovarian Cancer Cell Lines," 12 Mol. Cell. Biol. 9:3689-3698.
Hughes et al. (1992), "Purification of Nuclear Proteins That Bind to Cisplatin-Damaged DNA," 267 J. Biol. Chem. 13520-13527.
Pil et al. (1992), "Specific Binding of Chromosomal Protein HMG 1 to DNA Damaged by the Anticancer Drug Cisplatin," 256 Science 234-237.
Bruhn et al. (1992), "Isolation and Characterization of Human cDNA Clones Encoding a High Mobility Group Box Protein That Recognizes Structural Distortions to DNA Caused by Binding of the Anticancer Agent Cisplatin," 89 Proc. Nat'l. Acad. Sci. USA 2307-2311.
Donahue et al. (1991), "A Protein From Mammalian Cells That Recognizes Platinated DNA," Platinum and Other Metal Coord. Compounds in Cancer Chemotherapy, 241-251.
Jones et al. (1991), "Gene-Specific Formation and Repair of Cisplatin Intrastrand Adducts and Interstrand Cross-Links in Chinese Hamster Ovary Cells," 266 J. Biol. Chem. 11:7101-7107.
Sorenson et al. (1990), "Analysis of Events Associated With Cell Cycle Arrest at G2 Phase and Cell Death Induced by Cisplatin," 82 J. Natl. Cancer Inst. 9:749-755.
Donahue et al. (1990), "Characterization of a DNA Damage-Recognition Protein From Mammalian Cells That Binds Specifically to Intrastrand d(GpG) and d(ApG
Croy Robert G.
Essigmann John M.
Morningstar Marshall
Yarema Kevin J.
Brusca John S.
Ketter James
Massachusetts Institute of Technology
LandOfFree
Programmable genotoxic agents and uses therefor does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Programmable genotoxic agents and uses therefor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Programmable genotoxic agents and uses therefor will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1319836