Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-07-03
2000-04-25
Knode, Marian C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 46, 514 47, 514 48, 514 49, 514 50, 514 51, 536 278, 536 2781, 536 2712, 536 272, 536 2626, 435 6, A61K 3170, C07H 1914
Patent
active
060544422
ABSTRACT:
It was found that normal human stem cells produce a regulated non-processive telomerase activity, while cancer cells produce a processive telomerase activity. Nucleotide analogs, such as 7-deaza-2'-deoxyquanosine-5'-triphosphate (7-deaza-dGTP) were found to be substrates for processive telomerase and incorporated into telomeric sequence. The incorporation of this nucleotide subsequently affected the processivity of telomerase, converting processive telomerase to non-processive telomerase. The incorporation of this nucleotide analogs was also found to inhibit formation of G-quartets by telomeric sequence. Other methods for converting cancer processive telomerase to the more benign non-processive telomerase include partially cleaving the telomerase RNA. The nucleoside analogs were found to be capable of a variety of activities including mediating allosteric-like inhibition of telomerase, premature termination and shortening of telomeric DNA, destabilization of telomeric structure and function and eventually cell death. Understanding the mechanisms of telomerase modulation by the 7-deaza-nucleotides has allowed the design of new telomerase inhibitors, modulators and agents for affecting telomere structure and function. These discoveries have application in the treatment of cancer.
REFERENCES:
patent: 5091310 (1992-02-01), Innis
patent: 5446139 (1995-08-01), Seela et al.
patent: 5480980 (1996-01-01), Seela
patent: 5489508 (1996-02-01), West et al.
patent: 5654286 (1997-08-01), Hostetler
patent: 5656638 (1997-08-01), Gaeta et al.
patent: 5661148 (1997-08-01), Sakuma et al.
Allshire et al., "Human telomeres contain at least three types of G-rich repeat distributed non-randomly," Nucleic Acids Res., 17(12):4611-4627, 1989.
Allsopp et al., "Telomere length predicts replicative capacity of human firbroblasts," Proc. Natl. Acad., Sci. USA, 89:10114-10118, (Nov. 1992).
Bahler et al., Chromosoma 103, 129-141, 1994.
Balagutumoorthy and Brahmachari, J. Biol. Chem. 269, 21858-21869, 1994., (Aug. 26).
Baroin et al., "Telomeric site position heterogeneity in macronuclear DNA of Paramecium primaurelia," Nucleic Acids Res., 15(4):1717-1728, 1987.
Blackburn, "Telomerases," Annu. Rev. Biochem., 61:113-129, 1992.
Blackburn, "Telomeres sans frontieres," Nature, 343(11):122, (Jan. 11, 1990).
Blackburn, "Telomeres: Structure and Synthesis," J. Biol. Chem., 265(11):5919-5921, 1990.(Apr. 15).
Blackburn, "Telomeres and their synthesis," Science, 249:489-490, (Aug. 3, 1990).
Budarf and Blackburn, "S1 nuclease sensitivity of a double-stranded telomeric DNA sequence," Nucleic Acids Res., 15(15):6273-6292, 1987.
Carlson et al., "Evolution of the dispersed SUC gene family of Saccharomyces by rearrangements of chromosome telomeres," Mol. Cell. Biol., 5(11):2894-2902, (Nov. 1985).
Chadeneau et al., Cancer Res., 55:2533-2536, (Jun. 15, 1995).
Challoner and Blackburn, "Conservation of sequences adjacent to the telomeric C.sub.4 A.sub.2 repeats of ciliate macronuclear ribosomal RNA gene molecules," Nucleic Acids Res., 14(15):6299-6311, 1986.
Cherry and Blackburn, "The internally located telomeric sequences in the germ-line chromosomes of tetrahymena are at the ends of transposon-like elements," Cell, 43:747-758: 747-758, (Dec. 1985).
Chong et al., "A human telomeric protein," Science, 270:1663-1667, Dec. 8, 1995.
Cohn and Blackburn, "Telomerase in yeast," Science 269, 396-400, (Jul. 21, 1995).
Collins and Greider, "Utilization of ribonucleotides and RNA primers by Tetrahymena telomerase," EMBO J., 14:5422-5432, 1995.
Counter et al., "Telomerase activity in human ovarian carcinoma," Proc. Natl. Acad. Sci., 91:2900-2904, (Apr. 1994).
Counter et al., "Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity," EMBO J., 11:1921-1929, 1992.
Counter et al. "Telomere activity in normal leukocytes and in hematologic malignancies," Blood, 85:2315-2320, (May 1, 1995).
Doggett et al., "The Huntington disease locus is most likely within 325 kilobases of the chromosome 4p telomere," Proc. Natl. Acad. Sci. USA, 86:10011-10014, 1989(Dec.).
Dunn et al., "Transfer of yeast telomeres to linear plasmids by recombination," Cell, 39:191-201, (Nov. 1984).
Game, "Use of a ring chromosome and pulsed-field gels to study interhomolog recombination, double-strand DNA breaks and sister-chromatid exchange in yeast," Genetics, 123:695-713, (Dec. 1989).
Greider and Blackburn, "A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeast synthesis," Nature, 337(6205):331-337, (Jan. 26, 1989).
Greider and Blackburn, "Identification of a specific telomere terminal transferase activity in tetrahymena extracts," Cell, 43:405-413, (Dec. 1985).
Greider and Blackburn, "The telomere terminal transferase of tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity," Cell, 51:887-898, 1987. (Dec.).
Greider, "Telomeres, Telomerase and Senescence," BioEssays, 12(8):363-369, 1990(Aug.).
Greider, "Chromosome first aid," Cell, 67:645-647, (Nov. 5, 1991).
Gualberto et al., "Nucleic acid specificity of a vertebrate telomere-binding protein: evidence for G-G base pair recognition at the core-binding site," Genes & Development, 6:815-824, 1992.
Haber and Thorburn, "Healing of broken linear dicentric chromosomes in yeast," Genetics, 106:207-226, (Feb. 1984).
Haber et al., "Meiotic and mitotic behavior of dicentric chromosomes in Saccharomyces cerevisiae," Genetics, 106:185-205, (Feb. 1984).
Hardy et al., "A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation," Genes & Development, 6:801-814, 1992.
Hardesty et al., "Disposition of the Antitumor Agent Sangivamycin," Chemical Abstracts, 81(9), Abstract No. 45178, 1974 and Cancer Res., 34:1005-1009, 1974.
Harrington and Greider, "Telomerase primer specificity and chromosome healing," Nature, 353:451-454, (Oct. 3, 1991).
Herrick et al., "Mobile elements bounded by C.sub.4 A.sub.4 telomeric repeats in oxytricha fallax," Cell, 43:759-768, (Dec. 1985).
Hunter et al., "Precise excision of telomere-bearing transposons during oxytricha fallax macronuclear development," Genes & Development, 3:2101-2112, 1989.
International Search Report, PCT/US97/02279, Jan. 23, 1997, see "L".
Jager and Philippsen, "Stabilization of dicentric chromosones in Saccharomyces cerevisiae by telomere addition to broken ends or by centromere deletion," The EMBO Journal, 8(1):247-254, 1989.
Kang et al., "Crystal structure of four-stranded oxytricha telomeric DNA," Nature, 356:126-131, (Mar. 12, 1992).
Katinka and Bourgain, "Interstitial telomeres are hotspots for illegitimate recombination with DNA molecules injected into the macronucleus of Paramecium primaurelia," The EMBO Journal, 11(2):725-732, 1992.
Kim, et al., "Specific association of human telomerase activity with immortal cells and cancer," Science, 266:2011-2014, (Dec. 23, 1994).
King and Yao, "Tandemly repeated hexanucleotide at tetrahymena rDNA free end is generated from a single copy during development," Cell, 31:177-182, (Nov. 1982).
Kipling and Cooke, "Beginning or end? Telomere structure, genetics and biology," Human Molecular Genetics, 1(1):3-6, 1992.
Klingelhutz et al., "Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells," Mol. Cell Biol., 14:961-969, (Feb. 1994).
Lange, et al., "Structure and variability of human chromosome ends," Mol. Cell. Biol. 10(2):518-527, (Feb. 1990).
Larson et al., "Dynamics of telomere length variation in tetrahymena thermophila," Cell, 50:477-483, (Jul. 31, 1987).
Lee and Blackburn, "Sequence-specific DNA primer effects on telomerase polymerization activity," Molecular and Cellular Biology, 13(10):6586-6599, (Oct. 1993).
Liu and Gilbert, "The yeast KEM1 gene encodes a nuclease specific for G$ tetraplex DNA: Implication on in vivo functions for this novel DNA structure," Cell, 77:083-1092, 1994. (Jul. 1).
Liu and Gilbert, "Gene disruption of a G4-DNA-dependent nuclease in yeast leads to cellular senescence and telomere shortening," Proc. Natl. Acad., Sci. USA,
Chen Shih-Fong
Fletcher Terace M.
Kerwin Sean M.
Maine Ira
Mamiya Blain
Board of Regents University of Texas System
Crane L. Eric
CTRC Research Foundation
Knode Marian C.
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