Substituted purines and oligonucleotide cross-linking

Details Substituted purines and oligonucleotide cross-linking Substituted purines and oligonucleotide cross-linking

1997-10-09

1998-09-22

Wilson, James O.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 221, 536 253, 536 2534, 536 2626, 536 267, 544264, C07H 2100, C07H 1916

Patent

active

058115340

ABSTRACT:
This invention is directed to novel purine-based compounds for inclusion into oligonucleotides. The compounds of the invention, when incorporated into oligonucleotides are especially useful as "antisense" agents--agents that are capable of specific hybridization with a nucleotide sequence of an RNA. The compounds of the invention may also be used for cross-linking oligonucleotides. Oligonucleotides are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins, and cleaving RNA in site specific fashions. The compounds of the invention include novel heterocyclic bases, nucleosides, and nucleotides. When incorporated into oligonucleotides, the compounds of the invention can be useful for modulating the activity of RNA.

REFERENCES:
patent: 3666856 (1972-05-01), Elion et al.
patent: 3758684 (1973-09-01), Elion et al.
patent: 3919193 (1975-11-01), Mian et al.
patent: 4048307 (1977-09-01), Yokota et al.
patent: 4081534 (1978-03-01), Elion et al.
patent: 4123610 (1978-10-01), Summerton et al.
patent: 4230698 (1980-10-01), Bobek et al.
patent: 4321366 (1982-03-01), Bobek et al.
patent: 4369181 (1983-01-01), Miller et al.
patent: 4381344 (1983-04-01), Rideout et al.
patent: 4481197 (1984-11-01), Rideout et al.
patent: 4751221 (1988-06-01), Watanabe et al.
patent: 4751292 (1988-06-01), Fox
patent: 4751293 (1988-06-01), Kataoka et al.
patent: 4755594 (1988-07-01), Bridges et al.
patent: 5378825 (1995-01-01), Cook et al.
patent: 5459255 (1995-10-01), Cook et al.
patent: 5681941 (1997-10-01), Cook et al.
Atherton et al., "The Fluorenylmethoxycarbonyl Amino Protecting Group", The Peptides, Gross and Meienhofer (eds.), Academic Press, New York, 1987, 9, 1-38.
Beaucage et al., "Deoxynucleoside Phosphoramidites -A New Class of Key Intermediates for Deoxypolynucleotide Synthesis", Tetra Lett., 1981, 22(20), 1859-1862.
Beaucage, S.L. et al., "Advances in the Synthesis of Oligonucleotides by the Phosphoramidite Approach", Tetrahedron, 1992, 48, 2223-2311.
Blackburn & Gait (eds.), Nucleic Acids in Chemistry and Biology, Oxford University Press, New York, 1991.
Caruthers, "Synthesis of Oligonucleotides and Oligonucleotide Analogues", J.S. Cohen (ed.), CRC Press, Inc., Boca Raton, Florida, 1989, 7-24.
Casale et al., "Synthesis and Properties of an Oligodeoxynucleotide Containing a Polycyclic Aromatic Hydrocarbon Site Specifically Bound to the N.sup.2 Amino Group of a 2'-Deoxyguanosine Residue", J. Am. Chem. Soc., 1990, 112, 5264-5271.
Christalli, G. et al., "Synthesis of 2-Azido-(R) -N.sup.6 -p-Hydroxyphenylisopropyladenosine (R-Ahpia) as Potential Photoaffinity Probe for A.sub.1 Adenosine Receptors", Nucleosides & Nucleotides, 1986, 5, 213-222.
Cohen (ed.), Oligonucleotides: Antisense Inhibitors of Gene Express, CRC Press, Inc., Boca Raton, FL, 1989.
Cook, P.D., "Medicinal Chemistry Strategies for Antisense Research, in Antisense Research & Applications", Crooke et al. (ed.), CRC Press, Inc., Boca Raton, FL, 1993.
Cook, "Medicinal chemistry of antisense oligonucleotides-future opportunities", Anti-Cancer Drug Design, 1991, 6, 585-607.
Dagle et al., "Pathways of Degradation and Mechanism of Action of Antisense Oligonucleotides in Xenopus laevis Embryos", Antisense Res. Develop., 1991, 1, 11-20.
Dreyer et al., "Sequence-specific cleavage of single-stranded DNA: Oligonucleotide-EDTA.Fe(II)", Proc. Natl. Acad. Sci., 1985, 82, 968-972.
Ferentz et al., "Disulfide Cross-Linked Oligonucleotides", J. Am. Chem. Soc., 1991, 113, 4000-4002.
Ferentz, A.E. et al., "Aminolysis of 2'-Deoxyinosine Aryl Ethers: Nucleoside Model Studies for the Synthesis of Functionally Tethered Oligonucleotides", Nucleosides and Nucleotides, 1992, 11, 1749-1763.
Gaffney, B.L. et al., "Synthesis of O-6-Alkylated Deoxyguanosine Nucleosides", Tetra. Lett., 1982, 23, 2253-2256.
Gao et al., "6-O-(Pentafluorophenyl)-2'-deoxyguanosine: A Versatile Synthon for Nucleoside and Oligonucleotide Synthesis", J. Org. Chem., 1992, 57(25), 6954-6959.
Gmeiner, W.J. et al., "Development of an Efficient Oligonucleotide Derivatization Protocol", Bioorg. Med. Chem. Lett., 1991, 1, 487-490.
Greene and Wuts, Protection Groups in Organic Synthesis, 2d edition, John Wiley & Sons, New York, 1991.
Grineva et al., "Complementary Addressed Modification of rRNA with p-(Chloroethylmethylamino)Benzylidene Hexanucleotides", FEBS Letters, 1973, 32(2), 351-355.
Haralambidis et al., "Preparation of base-modified nucleosides suitable for non-radioactive label attachment and their incorporation into synthetic oligodeoxyribonucleotides", Nucl. Acids Res., 1987, 15(12), 4856-4876.
Harris et al., "New Strategy for the Synthesis of Oligonucleotides Bearing Adducts at Exocyclic Amino Sites of Purine Nucleosided", J. Am. Chem. Soc., 1991,113, 4328-4329.
Hayakawa, H. et al., "A Lithiation Approach to Cordycepin Analogues Variously Substituted at the C-8 Position", J. Het. Chem., 1989, 26, 189-192.
Hayakawa, H. et al., "Direct C-8 Lithiation of Naturally-Occurring Purine Nucleosides. A Simple Method for the Synthesis of 8-Carbon-Substituted Purine Nucleosides", Chem. Pharm. Bull., 1987, 35, 72-79.
Hirota, K. et al., "Convenient Method for the synthesis of C-Alkylated Purine Nucleosides: Palladium-Catalyzed Cross-Coupling Reaction of Halogenopurine Nuclosides with Trialkylaluminums", J. Org. Chem., 1992, 57, 5268-5270.
Horn et al., "Controlled Chemical Cleavage of Synthetic DNA at Specific Site", Nucleosides & Nucleotides, 1991, 10(1-3), 299-302.
Inoue et al., "Synthesis and hybridization studies on two complementary nona(2'-O-methyl)ribonucleotides", Nucl. Acids Res., 1987, 15(15), 6131-6148.
Iyer et al., "Abasic oligodeoxyribonucleoside phosphorothioates: synthesis and evaluation as anti-HIV-1 agents", Nucl. Acids Res., 1990, 18(10), 2855-2859.
Iyer et al., "3H-1,2-Benzodithiole-3-one 1,1-Dioxide as an Improved Sulfurizing Reagent in the Solid-Phase Synthesis of Oligodeoxyribonucleoside Phosphorothioates", J. Am. Chem. Soc., 1990, 112, 1253-1254.
Johnson et al., "Site-Specific Adduct Formation in Oligomeric DNA Using a New Protecting Group", J. Am. Chem. Soc., 1992, 114, 4923-4924.
Kawasaki et al., "Uniformly Modified 2'-Deoxy-2'-fluoro Phosphorothioate Oligonucleotides as Nuclease-Resistant Antisense Compounds with High Affinity and Specificity for RNA Targets", J. Med. Chem., 1993, 36(7), 831-841.
Kim, S.J. et al., "A Postoligomerization Synthesis of Oligodeoxynucleotides Containing Polycyclic Aromatic Hydrocarbon Adducts at the N.sup.6 Position of Deoxyadenosine", J. Am. Chem. Soc., 1992, 114, 5480-5481.
Lee et al., "Syntheses of Polycyclic Aromatic Hydrocarbon-Nucleoside and Oligonucleotide Adducts Specifically Alkylated on the Amino Functions of Deoxyguanosine and Deoxyadenosine", Tetra. Lett., 1990, 31, 6773-6776.
Lesnik et al., "Oligodeoxynucleotides Containing 2'-O-Modified Adenosine: Synthesis and Effects on Stability of DNA:RNA Duplexes", Biochem., 1993, 32, 7832-7838.
Lindahl et al., "DNA N-Glycosidases", J. Biol. Chem., 1977, 252(10), 3286-3294.
Matsuda, A. et al., "Nucleosides & Nuceotides. 103. 2-Alkynyladenosienes:A Novel Class of Antihypertensive Effects", J. Med. Chem., 1992, 35, 241-252.
Matteucci et al., "Synthesis and Crosslinking Properties of a Deoxyoligonucleotide Containing N.sup.6,N.sup.6 -Ethanodeoxyadenosine", Tetra. Lett., 1987, 28(22), 2469-2472.
Meyer et al., "Efficient, Specific Cross-Linking and Cleavage of DNA by Stable, Synthetic Complementary Oligonucleotides", J. Am. Chem. Soc., 1989, 8517-8519.
Miller et al., "A new approach to chemotherapy based on molecular biology and nucleic acid chemistry: Matagen (masking tape for gene expression)", Anti-Cancer Drug Design, 1987, 2, 117-128.
Mirabelli et al., "In vitro and in vivo pharmacologic activities of antisense oligonucleotides", Anti-Cancer Design, 1991, 6, 647-661.
Motawia et al., "A New Route to 2',3'-Dideoxycytidine", Liebigs Ann. Chem., 1990, 599-602.
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