Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1996-08-15
1998-11-03
Jones, W. Gary
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 5, 435 911, 435 912, 536 253, 536 2433, 536 245, C12Q 168, C12Q 170, C12P 1934, C07H 2104
Patent
active
058306587
ABSTRACT:
The invention provides methods and compositons for convergent synthesis of branched polymers useful as molecular probes. The invention also includes several novel branched polymeric structures particularly useful for detecting target polynucleotides. Branched polymers of the invention comprise at least two branches: at least one branch is a target binding moiety capable of specifically binding to a target molecule of interest and one or more branches are signal generation moities capable of directly or indirectly generating a detectable signal. In accordance with the method of the invention branched polymers are assembled from components having phosphorothioate groups and/or haloacyl- or haloalkylamino groups. The phosphorothioate and haloacyl- or haloalkylamino groups react rapidly and efficiently when brought into contact to form thiophosphorylacyl- or thiophosphorylalkylamino bridges which complete the assembly of a branched polymer. The method of the invention permits thorough purification and isolation of the components prior to final assembly. Incomplete branched polymers are readily separated from the desired product by standard means. The method of the invention permits the synthesis of several novel branched polymer configurations.
REFERENCES:
patent: 4739044 (1988-04-01), Stabinsky
patent: 4775619 (1988-10-01), Urdea
patent: 4925785 (1990-05-01), Wang et al.
patent: 4948882 (1990-08-01), Ruth
patent: 4958013 (1990-09-01), Letsinger
patent: 5093232 (1992-03-01), Urdea et al.
patent: 5098890 (1992-03-01), Gewirtz et al.
patent: 5124246 (1992-06-01), Urdea et al.
patent: 5237019 (1993-08-01), Ghosh et al.
patent: 5245022 (1993-09-01), Weis et al.
patent: 5256775 (1993-10-01), Froehler
patent: 5476930 (1995-12-01), Letsinger
Horn et al. Nucleic Acids Research 17:6959-6967, 1989.
Agrawal et al, "Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus," Proc. Natl. Acad. Sci. USA, 85:7079-7083 (1988).
Chang et al, "Improved methods for the synthesis of branched DNA (bDNA) for use as amplification multimers in bioassays," Nucleosides & Nucleotides, 10:389-392 (1991).
Dagle et al, "Physical properties of oligonucleotides containing phosphoramidate-modified internucleoside linkages," Nucleic Acids Research, 19:1805-1810 (1991).
Dolinnaya et al, "Construction of branched DNA (bDNA) molecules by chemical ligation," Bioorganic & Medicinal Chemistry Letters, 4:1011-1018 (1994).
Francois et al, "Periodic cleavage of poly(dA) by oligothymidylates covelently linked to the 1, 10-phenanthroline-copper complex," Biochemistry, 28:261-267 (1989).
Grachev et al, "A route to RNA with an alkylating group at the 5'-triphosphate residue," Nucleic Acids Research 8:3413-3426 (1980).
Hodges et al, "Post-assay' covalent labeling of phosphorothioate-containing nucleic acids with multiple fluorescent markers," Biochemistry, 28:261-267 (1989).
Horn et al, "Solid supported chemical 5'-phosphorylation of oligodeoxyribonucleotides that can be monitored by trityl cation release: application to gene synthesis," Nucleosides & Nucleotides, 6:335-340 (1987).
Horn et al, "The synthesis of branched oligonucleotides as signal amplification multimers for use in nucleic acid assays," Nucleosides & Nucleotides, 8:875-877 (1989).
Le Doan et al, "Sequence-specific recognition, photocrosslinking and covalently linked to an azidoproflavine derivative," Nucleic Acids Research, 15:7749-7760 (1987).
Milligan et al, "Current concepts in antisense drug design," Journal of Medicinal Chemistry, 36:1923-1937 (1993).
Oshevski et al, "Enzymatic transfer of ATP.sub..gamma. S thiophosphate onto the 5'hydroxyl of an oligonucleotide as a route to reactive oligonucleotide derivatives," FEBS Letters, 143:119-123 (1982).
Praseuth et al, "SeqUence-spEcific binding and photocrosslinking of .alpha. and .beta. oligodeoxynucleotides to the major groove of DNA via triple-helix formation," Proc. Natl. Acad. Sci. USA, 85:1349-1353 (1988).
Fidanza et al, "Introduction of reporter groups at specific sites in DNA containing phosphorothioate diesters," Journal of American Chemical Society, 111:9117-9119 (1989).
Uhlmann et al, Chemical Reviews, 90:567-569 & 575 (1990).
Rothenberg et al, Journal of the National Cancer Institute, 81:1539-1544 (1989).
Simons et al, Nature, 359-67-70 (1992).
Fahy et al, Nucleic Acids Research, 21:1819-1826 (1993).
Prakash et al, "Structural effect in the recognition of DNA by circular oligonucleotides," J. Am. Chem. Soc., 114:3523-3527 (1992).
Salunkhe et al, "Control of folding and binding of oligonucleotides by use of a nonnucleotide linker," J. Am. Chem. Soc., 114:8766-8772 (1992).
Reed et al, "Acridine- and cholesterol-derivatized solid supports for improved synthsys of 3'-moified oligonucleotides," Bioconjugate Chem. 2:217-225 (1991).
Froehler et al, "Phosphoramidate analogues of DNA: synthesis and thermal stability of heteroduplexes," Nucleic Acids Research, 16:4831-4839 (1988).
Agrawal et al, "Site specific functionalization of oligonucleotides for attaching two different reporter groups," Nucleic Acids Research, 18:5419-5423 (1990).
Durand et al, "Circular dichroism studies of an oligonucleotide containing a hairpin loop made of a hexaethylene glycol chain: conformation," Nucleic Acids Research, 18:6353-6359 (1990).
Roberts et al, "Specificity and stringency in DNA triplex formation," Proc. Natl. Acad. Sci. USA, 88:9397-9401 (1991).
Ma et al, "Design and synthesis of RNA miniduplexes via a synthetic linker approach," Biochemistry, 32:1751-1758 (1993).
Agrawal et al, "Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling," Tetrahedron Letters, 31:1543-1546 (1990).
Zuber et al, "Enhanced ligation of DNA with a synthetic effector molecule," J. Am. Chem. Soc., 115:4939-4940 (1993).
Hudson et al. "Nucleic acid dendrimers: novel biopolymer structures." J. Am. Chem. Soc., 115:2119-2124 (1993).
Gryaznov et al, "Anchor for one step release of 3'-aminooligonucleotides from a solid support," Tetrahedron Letters, 34:1261-1264 (1993).
Gryaznov et al, "Template controlled coupling and recombination of oligonucleotide blocks containing thiophosphoryl groups," Nucleic Acids Research, 21:1403-1408 (1993).
Gryaznov et al, "Synthesis and properties of oligonucleotides containing aminodeoxythymidine units," Nucleic Acids Research, 20:3403-3409 (1992).
Horn et al, "Forks and combs and DNA: the synthesis of branched oligodeoxyribonucleotides," Nucleic Acids Research, 17:6959-6967 (1989).
MacKellar et al, "Synthesis and physical properties of anti-HIV antisense oligonucleotides bearing terminal lipophilic groups," Nucleic Acids Research, 20:2411-2417 (1992).
Goodchild, "Conjugates of oligonucleotides and modified oligonucleotides: a review of their synthesis and properties," Bioconjugate Chem., 1:165-187 (1990).
Clontech Laboratories, 1989-1990 Catalog (excerpt).
Ashley et al, "Chemical synthesis of oligonucleotide dumbbells," Biochemistry, 30:2927-2933 (1991).
Jager et al, "Oligonucleotide N-alkylphosphoramidates: synthesis and binding to polynucleotides," Biochemistry, 27:7237-7246 (1988).
Jaschke et al, "Automated incorporation of polyethylene glycol into synthetic oligonucleotides," Tetrahedron Letters, 34:301-304 (1993).
Will et al, "Attachment of vitamin E derivatives to oligonucleotides during solid-phase synthesis," Tetrahedron Letters, 33:2729-2732 (1992).
Letsinger et al, "Synthesis and properties of modified oligonucleotides," Nucleic Acids Research, Symposium Series No. 24:75-78 (1991).
Haralambidis et al, "The synthesis of polyamide-oligonucleotide conjugates molecules," Nucleic Acids Research, 18:493-505 (1990).
Letsinger et al, "Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture," Proc. Natl. Acad. Sci., 86:6553-6556 (1989).
Shea et al, "Synthesis, hybridization properties and antiviral activity of lipid-oligonucleotide conjugates," Nucleic Acids Research, 18:3777-3783 (1990).
Newton et al, "The production of PCR products with 5' sin
Jones W. Gary
Lynx Therapeutics, Inc.
Macevicz Stephen C.
Rees Dianne
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