Sequence selective binding of bis-daunorubicin WP631 to DNA.

We have used footprinting techniques on a wide range of natural and synthetic footprinting substrates to examine the sequence-selective interaction of the bis-daunorubicin antibiotic WP631 with DNA. The ligand produces clear DNase I footprints that are very different from those seen with other anthracycline antibiotics such as daunorubicin and nogalamycin. Footprints are found in a diverse range of sequences, many of which are rich in GT (AC) or GA (TC) residues. As expected, the ligand binds well to the sequences CGTACG and CGATCG, but clear footprints are also found at hexanucleotide sequences such GCATGC and GCTAGC. The various footprints do not contain any particular unique di-, tri- or tetranucleotide sequences, but are frequently contain the sequence (G/C)(A/T)(A/T)(G/C). All sequences with this composition are protected by the ligand, though it can also bind to some sites that differ from this consensus by one base pair.

[1]  G. Shaw,et al.  Bis-Anthracycline Antibiotics Inhibit Human Immunodeficiency Virus Type 1 Transcription , 2004, Antimicrobial Agents and Chemotherapy.

[2]  B. Aggarwal,et al.  Evidence that activation of nuclear factor-kappaB is essential for the cytotoxic effects of doxorubicin and its analogues. , 2004, Biochemical pharmacology.

[3]  R. Brownlee,et al.  Bis-daunomycin hydrazones: Interactions with DNA , 1992, Investigational New Drugs.

[4]  H. Kozłowski,et al.  New findings in the study on the intercalation of bisdaunorubicin and its monomeric analogues with naked and nucleus DNA. , 2003, Chemico-biological interactions.

[5]  R. Lokey,et al.  Design, synthesis, and characterization of polyintercalating ligands. , 2002, Methods in enzymology.

[6]  K. Fox,et al.  Preferred binding sites for [N-MeCYs(3), N-MeCys(7)]TANDEM determined using a universal footprinting substrate. , 2001, Analytical biochemistry.

[7]  M. Waring,et al.  High-resolution footprinting studies of drug-DNA complexes using chemical and enzymatic probes. , 2001, Methods in enzymology.

[8]  A. Vaquero,et al.  Analysis of the effects of daunorubicin and WP631 on transcription. , 2001, Current medicinal chemistry.

[9]  J. Chaires,et al.  Exploiting anthracycline scaffold for designing DNA-targeting agents. , 2001, Methods in enzymology.

[10]  D. Gowers,et al.  Secondary binding sites for triplex-forming oligonucleotides containing bulges, loops, and mismatches in the third strand , 2000 .

[11]  K R Fox,et al.  Targeting DNA with triplexes. , 2000, Current medicinal chemistry.

[12]  D E Wemmer,et al.  Designed sequence-specific minor groove ligands. , 2000, Annual review of biophysics and biomolecular structure.

[13]  R. Bürli,et al.  Sequence-specific DNA recognition by polyamides. , 1999, Current opinion in chemical biology.

[14]  A. Vaquero,et al.  Bisanthracycline WP631 inhibits basal and Sp1-activated transcription initiation in vitro. , 1999, Nucleic acids research.

[15]  J. Chaires.  Drug--DNA interactions. , 1998, Current opinion in structural biology.

[16]  J. Chaires,et al.  Ultratight DNA binding of a new bisintercalating anthracycline antibiotic. , 1998, Biochemistry.

[17]  A. Wang,et al.  Binding of two novel bisdaunorubicins to DNA studied by NMR spectroscopy. , 1997, Biochemistry.

[18]  J. Chaires,et al.  Structure of a DNA-bisdaunomycin complex. , 1997, Biochemistry.

[19]  R. Perez-soler,et al.  Structure-based design of a new bisintercalating anthracycline antibiotic. , 1997, Journal of medicinal chemistry.

[20]  J. Chaires.  Molecular recognition of DNA by Daunorubicin , 1996 .

[21]  W. Priebe.  Anthracycline antibiotics : new analogues, methods of delivery, and mechanisms of action , 1994 .

[22]  T. Stonehouse,et al.  DNase I footprinting of triple helix formation at polypurine tracts by acridine-linked oligopyrimidines: stringency, structural changes and interaction with minor groove binding ligands. , 1994, Biochimica et biophysica acta.

[23]  N. Thuong,et al.  Sequence‐Specific Recognition and Modification of Double‐Helical DNA by Oligonucleotides , 1993 .

[24]  R. Weiss.  The anthracyclines: will we ever find a better doxorubicin? , 1992, Seminars in oncology.

[25]  C. M. Nunn,et al.  DNA-drug interactions. The crystal structures of d(TGTACA) and d(TGATCA) complexed with daunomycin. , 1991, Journal of molecular biology.

[26]  M. Waring,et al.  Preferential binding of daunomycin to 5'ATCG and 5'ATGC sequences revealed by footprinting titration experiments. , 1990, Biochemistry.

[27]  M. Churchill,et al.  Detection of drug binding to DNA by hydroxyl radical footprinting. Relationship of distamycin binding sites to DNA structure and positioned nucleosomes on 5S RNA genes of Xenopus. , 1990, Biochemistry.

[28]  A. Rich,et al.  Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin. , 1990, Biochemistry.

[29]  O Kennard,et al.  DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin. , 1991, Journal of molecular biology.

[30]  Fox Kr.  Footprinting studies on the interactions of nogalamycin, arugomycin, decilorubicin and viriplanin with DNA. , 1988 .

[31]  I. Kyratzis,et al.  The DNA-association and biological activity of a new bis(14-thiadaunomycin). , 1988, Anti-cancer drug design.

[32]  M. Waring,et al.  Diethyl pyrocarbonate can detect a modified DNA structure induced by the binding of quinoxaline antibiotics. , 1988, Nucleic acids research.

[33]  P. Nielsen,et al.  Detection of intercalation‐induced changes in DNA structure by reaction with diethyl pyrocarbonate or potassium permanganate Evidence against the induction of Hoogsteen base pairing by echinomycin , 1988, FEBS letters.

[34]  G. Grigg,et al.  Diethylpyrocarbonate and permanganate provide evidence for an unusual DNA conformation induced by binding of the antitumour antibiotics bleomycin and phleomycin. , 1988, Nucleic acids research.

[35]  J. Reiss,et al.  The 5′‐CA DNA‐sequence preference of daunomycin , 1988, FEBS letters.

[36]  M. Waring,et al.  Site and sequence specificity of the daunomycin-DNA interaction. , 1987, Biochemistry.

[37]  A. Rich,et al.  Interactions between an anthracycline antibiotic and DNA: molecular structure of daunomycin complexed to d(CpGpTpApCpG) at 1.2-A resolution. , 1987, Biochemistry.

[38]  M. Waring,et al.  Nucleotide sequence binding preferences of nogalamycin investigated by DNase I footprinting. , 1986, Biochemistry.

[39]  L. P. Wakelin,et al.  Polyfunctional DNA intercalating agents , 1986, Medicinal research reviews.

[40]  A. Rich,et al.  Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG). , 1980, Proceedings of the National Academy of Sciences of the United States of America.