Oligonucleotides and their analogs capable of passive cell membr

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving fixed or stabilized – nonliving microorganism,...

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536 221, 536 245, 536 243, 536 2431, C07H 2102, C07H 2104, A61K 3170

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057632081

ABSTRACT:
Oligonucleotides that are capable of passive diffusion across cell membranes are disclosed. These oligonucleotides contain at least two nucleotide residues and show a log distribution coefficient in octanol:water of about 0.0-2.5 and a solubility in water of at least 0.001 .mu.g/mL. In preferred embodiments, either at least 80% of the internucleotide linkages are non-ionic, or at least 80% of the bases contain lipophilic hydrocarbyl substitutions, or a combination of these sums to 80%. These oligonucleotides may be conjugated to label and used to visualize cells.

REFERENCES:
patent: 4904582 (1990-02-01), Tullis
patent: 4958013 (1990-09-01), Letsinger
patent: 5013830 (1991-05-01), Ohtsuka et al.
patent: 5264423 (1993-11-01), Cohen et al.
patent: 5420330 (1995-05-01), Brush
patent: 5633360 (1997-05-01), Bischofberger et al.
Clivio et al., "Synthesis of Dinucleoside Phosphates Containing Sulfur Substituted Nucleobases: 4-Thiouracil, 4-Thiothymine and 6-Mercaptopurine," Tet Lett 33:69-72 (1992).
Hobbs et al., "Polynucleotides Containing 2'-Amino-2'-deoxyribose and 2'-Azido-2'deoxyribose," Biochem 12:5138-5145 (1973).
Kumar et al., "Synthesis and Antiviral Activity of Novel 5-(1-Azido-2-haloethyl) and 5-(1-Azido-, amino-, or methoxyethyl) Analogs of 2'-Deoxyuridine," J Med Chem 36:2470-2474 (1993).
Lesnik et al., "Oligodeoxynucleotides Containing 2'-0-Modified Adenosine: Synthesis and Effects on Stability of DNA:RNA Duplexes," Biochem 32:7832-7838 (1993).
Mamos et al., "Straightforward C-8 alkylation of adenosine analogues with tetraalkltin reagents," Tet Lett p. 2413-2416 (1992).
Noonan et al., "Interaction of GTP Derivatives with Cellular and Oncogenic ras-p21 Proteins," J Med Chem 34:1302-1307 (1991).
Pudlo et al., "Synthesis, Antiproliferative, and Antiviral Activity of Certain 4-Substituted and 4,5-Disubstituted 33:1984-1992 (1990).
Ramasamy et al., "A Facile Synthesis of Tubercidin and Related 7-Deazapurine Nucleosides Via The Stereospecific Sodium Salt Glycosylation Procedure," Tet Lett 28(43):5107-5110 (1987).
Robins et al., "Nucleic Acid Related Compounds. 31. Smooth and Efficient Palladium-Copper Catalyzed Coupling of Terminal Alkynes with 5-Iodouracil Nucleosides," Tet Lett 22:421-424 (1981). an C-5--ein Weg zur Synthese von Aglycon-Analoga des Nucleosids,,Q", CHEM BER III pp. 2925-2930 (1978).
Seela et al., "Mannich-Reaktion am Ribonucleosids,,Q", Chem Ber 110:1462-1469 (1977).
Seela et al., "Synthese von Acyclo-7-desazaguanosin durch regiospezifische Phasentransferalkylierung von 137-146 (1993).
Seela et al., "Synthesis and Application of Isosteric Purine 2'-Deoxyribofuranosides," Nucls & Nuclt 6(1&2):11-23 (1987).
Sugawara et al., "Studies on the Chemical Synthesis of Potential Antimetabolites. 32. Synthesis of Beta-D-Pentofuranosyldeazaadenines as Candidate Inhibitors for S-Adenosylhomocysteinases and Methyltransferases," Nucls & Nuclt 1(3):239-251 (1982).
Townsend et al., "The Synthesis of (7-Deazaguanosine), a Nucleoside Q and Q* Analog," J HET CHEM 13:1363-1364 (1976).
Winkeler et al., "Synthesis of 2-Amino-7-(2'deoxy-beta-D-erythro-pentofuranosyl)-3,7 2'-Deoxyguanosine," J Org Chem 48:3119-3122 (1983).
Wright et al., "Deoxyribonucleotide Analogs as Inhibitors and Substrates of DNA Polymerase," Pharmaceutical Technology 47:447-497 (1990).
Divakar et al., "Reaction Between 2,2'-Anhydro-1-beta-o-arabinofuranosyluracil and Thiolate Ions," J Chem Soc Perkin Trans I pp. 1625-1628 (1982).
Rottman et al., "Influence of 2'-O-Alkylation on the Structure of Single-Stranded Polynucleotides and the Stability of 2'O-Alkylated Polynucleotide Complexes," BIOCHEM 13(13):2762-2771 (1974).
Agrawal et al., "Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus," PROC NATL ACAD SCI 85:7079-7083 (1988).
Akhtar et al., "Interactions of antisense DNA oligonucleotide analogs with phospholipid membranes (liposomes)," NUC ACIDS RES 19:5551-5559 (1991).
Blencowe et al., "Antisense Probin of the Human U4/U6 snRNP with Biotinylated 2'-OMe RNA Oligonucleotides," Cell 59:531-539 (1989).
Chavis et al. "Synthesis of 2',3'-Differentiated Ribonucleosides via Glycosylation Reactions with 2-O-Me or 2-O-TBDMS Ribofuranose Derivatives. 1. Pyrimidine Series," J Org Chem 47:202-206 (1982).
Clare, Susan E., "Deoxyoligoribonucleotides Containing A Single, Site-Specific 2,2,2-Trichloro-1,1-Dimethylethyl Phosphotriester Bond,"
Codington et al., "Synthesis of 2'-Fluorothymidine, 2'-Fluorodeoxyuridine, and Other 2'-Halogeno-2'-Deoxy Nucleosides," J Org Chem 29:558-564 (1964).
Cotten et al., "2'-O-methyl, 2'-O-ehtyl oligoribonucleotides and phosphorothioate oligodeoxynucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event," Nuc Acids Res 19:2629-2635 (1991).
Dagle et al., "Physical properties of oligonucleotides containing phosphoramidate-modified internucleoside linkages," NUC ACIDS RES 19:1805-1810 (1991).
Diez et al., "Unique Amino Acid Substitutions in the Capsid Proteins of Foot-and-Mouth Disease Virus from a Persistent Infection in Cell Culture," J Virol 64:5519-5528 (1990).
Fazakerley et al., "A-.fwdarw. Z transition in the synthetic hexanucleotide (dCdGfl)3," FEBS 182:365-369 (1985).
Froehler et al., "Deoxynucleoside H-Phosphonate Diester Intermediates in the Synthesis of Internucleotide Phosphate Analogues," Tet Lett 27:5575-5578 (1986).
Froehler et al., "Phosphoramidate analogues of DNA: synthesis and thermal stability of heteroduplexes," Nuc Acids Res 16:4831-4839 (1988).
Froehler et al., "Synthesis of DNA via deoxynucleoside H-phosphonate intermediates," Nuc Acids Res 14:5399-5407 (1986).
Froehler et al., "The Use of Nucleoside H-Phosphonates in the Synthesis of Deoxyoligonucleotides," Nucls & Nuclt 6:287-291 (1987).
Guinosso et al., "Synthesis of the DNA Ligase-Adenylate Intermediate: Lysine (epsilon-amino)-Linked Adenosine Monophosphoramidate," NUCLS & NUCLT 10:259-262 (1991).
Haeuptle et al., "Translation arrest by oligodeoxynucleotide complementary to mRNA coding sequences yields polypeptides of predetermine length," Nuc Acids Res 14:1427-1448 (1986).
Hansch et al., "Linear Relationships between Lipophilic Character and Biological Activity of Drugs," J Pharm Sci 61:1-19 (1972).
Hobbs et al., "Palladium-Catlyzed Synthesis of Alkynylamino Nucleosides. A Universal Linker for Nucleic Acids," J Org Chem 54:3420-3422 (1989).
Hoke et al., "Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection," Nuc Acids Res 19:5743-5748 (1991).
Huang et al., "Building Blocks for Oligonucleotide Analogues with Dimethylene Sulfide, Sulfoxide, and Sulfone Groups Replacing Phosphodiester Linkages," J Org Chem 56:3869-3882 (1991).
Huff et al. "DNA Damage at Thymine N-3 Abolishes Base-paring Capacity during DNA Synthesis," J Biol Chem 262(26):12843-12850 (1987).
Inoue et al., "Synthesis and hybridization studies on two complementary nona(2'-methyl)ribonucleotides," Nuc Acids Res 15:6131-6148 (1987).
Itoh et al, "A Novel Synthesis of 1-Deazaadenosine," Heterocycles 17:305-309 (1982).
Itoh et al, "Studies on the Chemical Synthesis of Potential Antimetabolites," NUCL & NUCLT 1(2):179-190 (1982).
Joshi et al., "Inhibition of Human Immunodeficiency Virus Type1 Multiplication by Antisense RNA Expression," J VIROL 65:5524-5530 (1991).
Kabanov et al., "A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus-specific proteins in MDCK cells," FEBS 259:327-330 (1990).
Lieb et al., "Biological Membranes behave as Non-porous Polymeric Sheets with Respect to the Diffusion of Non-electrolytes," Nature 224:240-243 (1969).
Loke et al., "Characterization of oligonucleotide transport into living cells," PROC NATL ACAD SCI 86:3474-3478 (1989).
Manoharan et al., "Novel Functionalization of the Sugar Moiety of Nucleic Acids for Multiple Labeling in the Minor Grove," Tet Lett 32:7171-7174 (1991).
Mizuno et al, "Synthetic Studies of Potential Antimetabolites. IX. Th

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