Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1994-04-22
2000-11-28
Riley, Jezia
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 231, 536 253, 536 2532, 536 266, 435 6, 514 1, 514 44, C07H 1900, C07H 2100, C12Q 168, A01N 4304
Patent
active
061537373
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This application is directed to sequence specific oligonucleotides that include functionalized nucleosides having substituents such as steroids, reporter molecules, reporter enzymes, non-aromatic lipophilic molecules, peptides, or proteins attached via linking groups.
BACKGROUND OF THE INVENTION
Messenger RNA (mRNA) directs protein synthesis. Antisense methodology is the complementary hybridization of relatively short oligonucleotides to mRNA or DNA such that the normal, essential functions of these intracellular nucleic acids are disrupted. Hybridization is the sequence-specific hydrogen bonding of oligonucleotides to RNA or single-stranded DNA via complementary Watson-Crick base pairs.
The naturally occurring events that provide the disruption of the nucleic acid function, discussed by Cohen in Oligonucleotides: Antisense Inhibitors of Gene Expression, CRC Press, Inc., Boca Raton, Fla. (1989), are thought to be of two types. The first, hybridization arrest, denotes a terminating event in which the oligonucleotide inhibitor binds to the target nucleic acid and thus prevents, by simple steric hindrance, the binding of essential proteins, most often ribosomes, to the nucleic acid. Methyl phosphonate oligonucleotides (see, e.g., Miller, et al., Anti-Cancer Drug Design 1987, 2, 117) and .alpha.-anomer oligonucleotides, the two most extensively studied antisense agents, are thought to disrupt nucleic acid function by hybridization arrest.
The second type of terminating event for antisense oligonucleotides involves the enzymatic cleavage of targeted RNA by intracellular RNase H. A 2'-deoxyribofuranosyl oligonucleotide or oligonucleotide analog hybridizes with the targeted RNA to form a duplex that activates the RNase H enzyme to cleave the RNA strand, thus destroying the normal function of the RNA. Phosphorothioate oligonucleotides provide the most prominent example of antisense agents that operate by this type of antisense terminating event.
Considerable research is being directed to the application of oligonucleotides and oligonucleotide analogs as antisense agents for diagnostics, research reagents, and therapeutics. At least for therapeutic purposes, the antisense oligonucleotides and oligonucleotide analogs must be transported across cell membranes or taken up by cells to express activity. One method for increasing membrane or cellular transport is by the attachment of a pendant lipophilic group.
Ramirez, et al., J. Am. Chem. Soc. 1982, 104:, 5483, introduced the phospholipid group 5'-O-(1,2-di-O-myristoyl-sn-glycero-3-phosphoryl) into the dimer TpT independently at the 3' and 5' positions. Subsequently Shea, et al., Nuc. Acids Res. 1990, 18, 3777, disclosed oligonucleotides having a 1,2-di-O-hexyldecyl-rac-glycerol group linked to a 5'-phosphate on the 5'-terminus of the oligonucleotide. Certain of the Shea, et. al. authors disclosed these and other compounds in patent application PCT/US90/01002. Another glucosyl phospholipid was disclosed by Guerra, et al., Tetrahedron Letters 1987, 28, 3581.
In other work, a cholesteryl group was attached to the inter-nucleotide linkage between the first and second nucleotides (from the 3' terminus) of an oligonucleotide. This work is disclosed in U.S. Pat. No. 4,958,013 and by Letsinger, et al., Proc. Natl. Acad. Sci. USA 1989, 86, 6553. The aromatic intercalating agent anthraquinone was attached to the 2' position of a sugar fragment of an oligonucleotide as reported by Yamana, et al., Bioconjugate Chem. 1990, 1, 319.
Lemairte, et al., Proc. Natl. Acad. Sci. USA 1986, 84, 648 and Leonetti, et al., Bioconjugate Chem. 1990, 1, 149, disclose modifying the 3' terminus of an oligonucleotide to include a 3'-terminal ribose sugar moiety. Poly(L-lysine) was linked to the oligonucleotide via periodate oxidation of this terminal ribose followed by reduction and coupling through a N-morpholine ring. Oligonucleotide-poly(L-lysine) conjugates are described in European Patent application 87109348.0, wherein the lysine residue was coupled to a 5' or 3' pho
REFERENCES:
patent: 3687808 (1972-08-01), Merigan, Jr. et al.
patent: 4910300 (1990-03-01), Urdea et al.
patent: 4958013 (1990-09-01), Letsinger
patent: 5015733 (1991-05-01), Smith et al.
patent: 5108921 (1992-04-01), Low et al.
patent: 5296350 (1994-03-01), Rokita et al.
patent: 5466786 (1995-11-01), Buhr et al.
patent: 5470967 (1995-11-01), Huie et al.
patent: 5578718 (1996-11-01), Cook et al.
Caruthers "Synthesis of oligonucleotides and oligonucleotide analogues" Antisense inhibitors of gene expression, pp. 7-24, J.S. Cohen ed., CRC press, Boca Raton, FL 1989.
Mitchell et al. "Boron trifluoride-methanol complex as a non-depurinating detritylating agent in DNA synthesis" Nucleic Acids research, vol. 18, No. 17, p. 5321, 1990.
Schwartz et al. "The DNA bending by Acetylaminofluorene residues and by apurinic sites" J. Mol. Biol. vol. 207, pp. 445-450, 1989.
Haralambidis et al (1987) Tetrahedron Lett. 28, 5199-5202.
Asseline et al (1984), Proc. Nat. Acad. Sci. USA, 81, 3297-3301.
Corey et al (1987) Science 238, 1401-1403.
Letsinger (1989) Proc. Nat. Acad. Sci. USA 86, 6553-6556.
Yamana et al (1990) Bioconjugate Chem. 1, 319-324.
Telser et al (1989) J. Am. Chem. Soc. 111, 6966-6967.
Dreyer et al (1985) Proc. Nat. Acad. Sci. USA 82, 968-972.
Jablonski et al. (1986) Nuc. Ac. Res. 14, 6115-6128.
Mori et al (1989) Nucleosides and Nucleotides 8, 649-657.
Asseline, U. et al., "Solid-Phase Preparation of 5'-3'-Heterobifunctional Oligodeoxyribonucleotides Using Modified Solid Supports," Tetrahedron 1992, 48, 1233-1254.
Asseline, U. et al., "Nucleic acid-binding molecules with high affinity and base sequence specificity: Intercalating agents covalently linked to oligodeoxynucleotides," Proc. Natl. Acad. Sci. USA 1984, 81, 3297-3301.
Atherton,E. et al., The Peptides, Gross and Meienhofer, Eds, Academic Press; New York, vol. 9:1-38, 1983.
Baker, B.F., "Decapitation of a 5'-Capped Oligoribonucleotide by o-Phenanthroline: CU(II)," J. Am. Chem. Soc. 1993, 115, 3378-3379.
Beaucage, S. et al., "Advances in the Synthesis of Oligonucleotides by the Phosphoramidite Approach," Tetrahedron 1992, 48, 2223-2311.
Bennett, C.F. et al., "Cationic Lipids Enhance Cellular Uptake and Activity of Phosphorothioate Antisense Oligonucleotides", Molecular Pharmacology 1991, 41, 1023-1033.
Betebenner, D.A., et al., "Hepatobiliary Delivery of Polyaminopolycarboxylate Chelates: Synthesis and Characterization of a Cholic Acid Conjugate of EDTA and Biodistribution and Imaging Studies with Its Indium-111 Chelate", Bioconjugate Chem. 1991, 2, 117-123.
Bischoff, R. et al., "Introduction of 5'-Terminal Functional Groups into Synthetic Oligonucleotides for Selective Immobilization," Analy. Biochem. 1987, 164, 336-344.
Blackburn, G. et al., "Studies in Phosphorylation. Part XXIX. The Synthesis of Dialkyl Phosphates from Monoalkyl Phosphonates: Direct Oxidative Esterification", J. Chem. Soc. 1966, 239-245.
Chiang, M.-Y. et al., "Antisense Oligonucleotides Inhibit Intercellular Adhesion Molecule 1 Expression by Two Distinct Mechanisms", J. of Biol. Chem. 1991, 266, 18162-18171.
Chollet, A., "Selective Attachment of Oligonucleotides to Interleukin-1 beta and Targeted Delivery to Cells", Nucleosides & Nucleotides 1990, 9, 957-966.
Cohen, J. in Oligonucleotides: Antisense Inhibitors of Gene Expression, CRC Press, Inc., Boca Raton, FL, pp. 1-255, 1989.
Corey, D. et al., "Sequence-Selective Hydrolysis of Duplex DNA by an Oligonucleotide-Directed Nuclease", J. Am. Chem. Soc. 1989, 111, 8523-8525.
Corey, D. et al., "Generation of a Hybrid Sequence-Specific Single-Stranded Deoxyribonuclease", Science 1987, 238, 1401-1403.
Damha, M. et al., "An Improved Procedure for Derivitization of Controlled-Pore Glass Beads for Solid-Phase Oligonucleotide Synthesis", Nuc. Acids Res. 1990, 18, 3813-3821.
Delgado, C. et al., "The Uses and Properties of PEG-Linked Proteins", Critical Reviews in Therapeutic Drug Carrier Systems 1992, 9, 249-304.
Dingwall, C., et al., "Protein Import Into the Cell Nucleus", Ann. Rev. Cell Biol. 19
Bennett Clarence Frank
Cook Phillip Dan
Manoharan Muthiah
ISIS Pharmaceuticals Inc.
Riley Jezia
LandOfFree
Derivatized oligonucleotides having improved uptake and other pr does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Derivatized oligonucleotides having improved uptake and other pr, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Derivatized oligonucleotides having improved uptake and other pr will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1726907