Reactive anthraquinone derivatives and conjugates thereof

Details Reactive anthraquinone derivatives and conjugates thereof Reactive anthraquinone derivatives and conjugates thereof

1995-04-11

1997-07-22

Horlick, Kenneth R.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

536 245, 536 243, 552265, 552267, C07H 2102, C07H 2104

Patent

active

056503997

ABSTRACT:
Anthraquinone derivatives are constructed for alkylation of target molecules. The anthraquinone derivative includes an anthraquinone ring system which has been modified by the addition of inducibly reactive substituents at positions on the ring system. The anthraquinone ring system can be selectively activated for alkylation of a target molecule. The substituents may be from 1 to 4 methyl groups, whereupon activation is achieved by a photochemical signal. In an additional alternative embodiment, the inducible reactive substituents may include both methyl groups and substituted methylene groups. In this embodiment, the activation of the anthraquinone derivative is achieved by photochemical and/or reductive signals. Alternatively, the substituents may be from 1 to 8 methyl groups modified to include a reactive group, whereupon activation is achieved by a chemical or enzymatic reductive signal. The anthraquinone derivatives of the invention may be used for non-specific modification of target molecules. Alternatively, the anthraquinone derivative may be further derivatized to permit specific modification of target molecules. The further derivatization of the anthraquinone includes attaching a probe to the anthraquinone ring system by way of a linking group. The probe is chosen to selectively localize to a target molecule, whereupon the anthraquinone derivative may be activated to react with and aklylate the target molecule. Also the process of employing such anthraquinone derivatives for use in vitro or in vivo for alkylating, specifically or non-specifically alkylating, target molecules.

REFERENCES:
patent: 4355012 (1982-10-01), Renfrew et al.
patent: 5292873 (1994-03-01), Rokita et al.
patent: 5296350 (1994-03-01), Rokita et al.
Landegren et al., "DNA Diagnostics-Molecular Techniques and Automation", Science, 242, 229 (1988).
Miller et al., "Oligonucleotide Inhibitors of Gene Expression in Living Cells: New Opportunities in Drug Design", Ann. Reports in Med. Chem., 23, 295 (1988).
Tolume et al., "Antimessenger Oligodeoxyribonucleotides: An Alternative to Antisense RNA for Artificial Regulation of Gene Expression--A Review", Gene, 72, 51-58 (1988).
Stein et al., "Oligodeoxyribonucleotides as Inhibitors of Gene Expression: A Review", Cancer Research, 48, 2659-2668 (1988).
Barton, "Metals and DNA: Molecular Left-Handed Complements", Science, 233, 727-734 (1986).
Dervan, "Design of Sequence-Specific DNA-Binding Molecules", Science, 232, 464-471 (1986).
Blake et al., "Hybridization Arrest of Globin Synthesis in Rabbit Reticulocyte Lysates and Cells by Oligodeoxyribonucleoside Methylphosphonates", Biochemistry, 24, 6139-6145 (1985).
Agrawal et al., "Oligodeoxynucleoside Phosphoramidates and Phosphorothioates as Inhibitors of Human Immunodeficiency Virus", Proc. Natl. Acad. Sci. USA, 85, 7079-7083 (1988).
Iverson et al., "Nonenzymatic Sequence-Specific Cleavage of Single-Stranded DNA to Nucleotide Resolution. DNA Methyl Thiolether Probes", J. Am. Chem. Soc., 109, 1241-1243 (1987).
Maher III et al., "Inhibition of DNA Binding Proteins by Oligonucleotide-Directed Triple Helix Formation", Science, 245, 725-730 (1989).
Griffin et al., "Recognition of Thymine-Adenine Base Pairs by Guanine in a Pyrimidine Triple Helix Motif", Science, 245, 967-971 (1989).
Strobel et al., "Site-Specific Cleavage of a Yeast Chromosome by Oligonucleotide-Directed Triple-Helix Formation", Science, 249, 73-75 (1990).
Symons, Nucleic Acid Probes, CRC Press, Inc., Boca Raton, Florida (1989).
Gamper et al., "Reverse Southern Hybridization", Nucl. Acids Res., 14, 9943-9954 (1986).
Knorre et al., "Complementary-Addressed (Sequence Specific) Modification of Nucleic Acids", Prog. Nucleic Acids Res. Mol. Biol., 32, 291-320 (1985).
Webb et al., "Sequence-Specific Crosslinking of Deoxyoligonucleotides via Hybridization-Triggered Alkylation", J. Am Chem. Soc., 108, 2764-2765 (1986).
Meyer et al., "Efficient, Specific Crosslinking and Cleavage of DNA by Stable, Synthetic Complementary Oligonucleotides", J. Am. Chem. Soc., 111, 8517-8519 (1989).
Van Houten et al., "Action Mechanism of ABC Excision Nuclease on a DNA Substrate Containing a Psoralen Crosslink at a Defined Position", Proc. Natl. Acad. Sci. USA, 83, 8077-8081 (1986).
Lee et al., "Interaction of Psoralen-Derivatized Oligodeoxyribonucleoside Methylphosphonates with Single-Stranded DNA", Biochemistry, 27, 3197-3203 (1988).
Chatterjee et al., "Inducible Alkylation of DNA Using an Oligonucleotide Quinone Conjugate", J. Am. Chem. Soc., 112, 6397-6399 (1990).
Ramage et al, "Solid Phase Peptide Synthesis: Fluoride Ion Release of Peptide from the Resin", Tet. Lett., 28, 4105-4108 (1987).
Mullen et al, "A New Fluoridolyzable Anchoring Linkage for Orthogonal Solid Phase Peptide Synthesis", J. Org. Chem., 53, 5240-5248 (1988).
Trahanovsky et al., "Observation of Reactive o-Quinodimethanes by Flow NMR", J. Am. Chem. Soc., 110, 6579-6581 (1988).
Angle et al, "p-Quinone Methide Initiated Cyclization Reactions", J. Am. Chem. Soc., 111, 1136-1138 (1989).
Wahl et al., "Northern and Southern Blots", Meth. Enzymol., 152, 572-573 (1987).
Higuchi et al., "DNA Typing from Single Hairs", Nature, 332, 543-546 (1988).
Conner et al., "Detection of Sickle Cell .beta..sup.s -Globin Allele by Hybridization with Synthetic Oligonucleotides", Proc. Natl. Acad. Sci. USA, 80, 278-282 (1983).
Gebeyehu et al., "Novel Biotinylated Nucleotide-Analogs for Labelling and Colormetric Detection of DNA", Nucl. Acids Res., 15, 4513-4534 (1987).
Jager et al., "Oligonucleotide N-Alkyl-phosphoramides: Synthesis and Boindoing to Polynucleotides", Biochemistry, 27, 7237-7246 (1988).
Cocuzza, "Total Synthesis of 7-Iodo-2',3'-Dideoxy-7-Deazpurine Nucleosides, Key Intermediates in the Preparation of Reagents for the Automated Sequencing of DNA", Tet. Lett., 29, 4061-4064 (1988).
Hanna et al., "Synthesis and Characterization of 5-[(4-Azidophenacyl)thio]uridine 5'-Triphosphate, a Cleavable Photo-Cross Linking Nucleotide Analogue", Biochemistry, 28, 5814-5820 (1989).
Gibson et al., "Synthesis and Application of Derivatizable Oligonucleotides", Nucl. Acids Res., 15, 6455-6467 (1987).
Nelson et al., "A New and Versatile Reagent for Incorporating Multiple Primary Aliphatic Amines Into Synthetic Oligonucleotides", Nucl. Acids Res., 17, 7179-7186 (1989).
Maniatis et al., Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (1982).
Raval et al., "Condensation of Succinic Anhydride with Phenols" J. Univ. Bombay, 7, Pt. 3, 184-188 (1938); Chemical Abstracts, 33, 3779 (1939).
Dreyer et al., "Sequence-Specific Cleavage of Single-Stranded DNA: Oligodeoxynucleotide-EDTA-Fe(II)", Proc. Natl. Acad. Sci. USA, 82, 968-972 (1985).
Chu et al., "Nonenzymatic Sequence-Specific Cleavage of Single-Stranded DNA", Proc. Natl. Acad. Sci. USA, 82, 963-967 (1985).
Mack et al., "Design and Chemical Synthesis of a Sequence-Specific DNA-Cleaving Protein", J. Am. Chem. Soc., 110, 7572-7574 (1988).
Remers, "Antineoplastic Agents", Ch. 8, Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry, 9th Ed. Delgado et al., eds. 313-353, J.B. Lippincott Co., Philadelphia.
Goodchild, "Conjugates of Oligonucleotides and Modified Oligonucleotides: A Review of Their Synthesis and Properties", Bioconjugate Chem., 1, 165-187 (1990).
Uhlmann et al., "Antisense Oligonucleotides: A New Therapeutic Principle", Chem. Rev., 90, 543-584 (1990).
Nielsen, "Sequence-Selective DNA Recognition by Synthetic Ligands", Bioconjugate Chem., 2, 1-12 (1991).
Englisch et al., "Chemically Modified Oligonucleotides as Probes and Inhibitors", Angew. Chem. Int. Ed. Engl., 30, 613-629 (1991).
Brakel, ed., Discoveries in Antisense Nucleic Acids, Gulf Publishing Co., Houston (1989).
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).
Lin et al., "Hybridization Properties of Deoxyoligonucleotides Containing Anthraquinone Pseudonucleosides", Nucl. Acids Res., 19, 311

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