intercalating agents

Summary

Summary: Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA.

Top Publications

  1. pmc Mechanical and structural properties of YOYO-1 complexed DNA
    Katrin Günther
    BioNanotechnology and Structure Formation Group, Department of Chemistry and Food Chemistry, Biotechnology Center, Technische Universitat Dresden, D 01062 Dresden, Germany
    Nucleic Acids Res 38:6526-32. 2010
  2. pmc Probing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates
    Liang Xue
    Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, South Carolina 29634, USA
    Biochemistry 49:5540-52. 2010
  3. ncbi Combining the best in triplex recognition: synthesis and nucleic acid binding of a BQQ-neomycin conjugate
    Dev P Arya
    Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, USA
    J Am Chem Soc 125:8070-1. 2003
  4. ncbi Crystal structures of Λ-[Ru(phen)₂dppz]²⁺ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes
    Hakan Niyazi
    Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK
    Nat Chem 4:621-8. 2012
  5. pmc Crystal structure of Δ-[Ru(bpy)₂dppz]²⁺ bound to mismatched DNA reveals side-by-side metalloinsertion and intercalation
    Hang Song
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Nat Chem 4:615-20. 2012
  6. pmc The mechanism of topoisomerase I poisoning by a camptothecin analog
    Bart L Staker
    deCODE Genetics, Incorporated, BioStructures Group, 7869 Northeast Day Road West, Bainbridge Island, WA 98110, USA
    Proc Natl Acad Sci U S A 99:15387-92. 2002
  7. ncbi Structure of the complex of [Ru(tpm)(dppz)py](2+) with a B-DNA oligonucleotide - a single-substituent binding switch for a metallo-intercalator
    Philip Waywell
    Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK
    Chemistry 16:2407-17. 2010
  8. ncbi Drug--DNA interactions
    J B Chaires
    Department of Biochemistry, University of Mississippi Medical Center, Jackson 39216 4505, USA
    Curr Opin Struct Biol 8:314-20. 1998
  9. ncbi Molecular recognition of a DNA:RNA hybrid: sub-nanomolar binding by a neomycin-methidium conjugate
    Nicholas N Shaw
    Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, USA
    Bioorg Med Chem Lett 18:4142-5. 2008
  10. ncbi Effects of electrostatic screening on the conformation of single DNA molecules confined in a nanochannel
    Ce Zhang
    Biophysics and Complex Fluids Group, Department of Physics, National University of Singapore, 2 Science Drive 3, Singapore
    J Chem Phys 128:225109. 2008

Research Grants

  1. DNA Methyltransferase Inhibition by Intercalating Agents
    Keith D Robertson; Fiscal Year: 2010
  2. SIDEROPHORES, ANALOGS AND BIOCONJUGATES
    Marvin Miller; Fiscal Year: 1999
  3. RNA-SPECIFIC LIGANDS: AN APPROACH TO NEW ANTIVIRALS
    PETER BEAL; Fiscal Year: 2003
  4. REACTIVE INTERMEDIATES OF CARCINOGENESIS OF PAHS
    KENNETH LAALI; Fiscal Year: 2004
  5. SPECIFICITY OF INTERCALATOR DIRECTED GENOTOXICITY
    Russell Anderson; Fiscal Year: 1993
  6. THERMODYNAMICS OF DNA CONFORMATION AND INTERACTIONS
    LUIS MARKY; Fiscal Year: 1999
  7. 13C AND OTHER NUCLEI NMR OF DNA AND DNA INTERACTIONS
    GEORGE LEVY; Fiscal Year: 1980
  8. DNA DAMAGE AND REPAIR BY ANTITUMOR AGENTS
    WARREN ROSS; Fiscal Year: 1990
  9. TARGETABLE FORMULATIONS FOR NOVEL ANTI-CANCER AGENTS
    Keelung Hong; Fiscal Year: 2001
  10. Anti-Inflammatory Bioconjugates
    Benjamin Bowen; Fiscal Year: 2008

Detail Information

Publications216 found, 100 shown here

  1. pmc Mechanical and structural properties of YOYO-1 complexed DNA
    Katrin Günther
    BioNanotechnology and Structure Formation Group, Department of Chemistry and Food Chemistry, Biotechnology Center, Technische Universitat Dresden, D 01062 Dresden, Germany
    Nucleic Acids Res 38:6526-32. 2010
    ..We expect that our assay, in which all the parameters are determined within a single experiment, will be beneficial for a large range of other DNA binding drugs...
  2. pmc Probing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates
    Liang Xue
    Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, South Carolina 29634, USA
    Biochemistry 49:5540-52. 2010
    ..The results described here suggest that the binding affinity of intercalator-neomycin conjugates for poly(dA).2poly(dT) increases as a function of the surface area of the intercalator moiety...
  3. ncbi Combining the best in triplex recognition: synthesis and nucleic acid binding of a BQQ-neomycin conjugate
    Dev P Arya
    Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, USA
    J Am Chem Soc 125:8070-1. 2003
    ..Modeling studies suggest a structure of neomycin bound to the larger W-H (Watson-Hoogsteen) groove with BQQ intercalated between the triplex bases...
  4. ncbi Crystal structures of Λ-[Ru(phen)₂dppz]²⁺ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes
    Hakan Niyazi
    Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK
    Nat Chem 4:621-8. 2012
    ..The TA/TA specificity of the perpendicular intercalation arises from the packing of phenanthroline ligands against the adenosine residue...
  5. pmc Crystal structure of Δ-[Ru(bpy)₂dppz]²⁺ bound to mismatched DNA reveals side-by-side metalloinsertion and intercalation
    Hang Song
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Nat Chem 4:615-20. 2012
    ..This structure attests to the generality of metalloinsertion and metallointercalation as DNA binding modes...
  6. pmc The mechanism of topoisomerase I poisoning by a camptothecin analog
    Bart L Staker
    deCODE Genetics, Incorporated, BioStructures Group, 7869 Northeast Day Road West, Bainbridge Island, WA 98110, USA
    Proc Natl Acad Sci U S A 99:15387-92. 2002
    ..The first class includes changes to residues that contribute to direct interactions with the drug, whereas a second class would alter interactions with the DNA and thereby destabilize the drug-binding site...
  7. ncbi Structure of the complex of [Ru(tpm)(dppz)py](2+) with a B-DNA oligonucleotide - a single-substituent binding switch for a metallo-intercalator
    Philip Waywell
    Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK
    Chemistry 16:2407-17. 2010
    ..These results indicate that complexes derived from these systems have the potential to function as sequence-specific light-switch systems...
  8. ncbi Drug--DNA interactions
    J B Chaires
    Department of Biochemistry, University of Mississippi Medical Center, Jackson 39216 4505, USA
    Curr Opin Struct Biol 8:314-20. 1998
    ....
  9. ncbi Molecular recognition of a DNA:RNA hybrid: sub-nanomolar binding by a neomycin-methidium conjugate
    Nicholas N Shaw
    Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, USA
    Bioorg Med Chem Lett 18:4142-5. 2008
    ..Spectroscopic methods: UV, CD, fluorescence, and calorimetric techniques: DSC and ITC were used to characterize the sub-nanomolar binding displayed by the conjugate for the DNA:RNA hybrid duplex, poly(dA):poly(rU)...
  10. ncbi Effects of electrostatic screening on the conformation of single DNA molecules confined in a nanochannel
    Ce Zhang
    Biophysics and Complex Fluids Group, Department of Physics, National University of Singapore, 2 Science Drive 3, Singapore
    J Chem Phys 128:225109. 2008
    ..It is proposed that this contraction results from a divalent counterion mediated attractive force between the segments of the DNA molecule...
  11. pmc Torsional sensing of small-molecule binding using magnetic tweezers
    Jan Lipfert
    Department of BioNanoScience, Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands
    Nucleic Acids Res 38:7122-32. 2010
    ..These insights into the torsional consequences of ligand binding can help elucidate the effects of small-molecule drugs in the cellular environment...
  12. pmc Screening helix-threading peptides for RNA binding using a thiazole orange displacement assay
    Malathy Krishnamurthy
    Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
    Bioorg Med Chem 16:8914-21. 2008
    ....
  13. pmc Structure determination of an intercalating ruthenium dipyridophenazine complex which kinks DNA by semiintercalation of a tetraazaphenanthrene ligand
    James P Hall
    Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, United Kingdom
    Proc Natl Acad Sci U S A 108:17610-4. 2011
    ..The result is noncovalent cross-linking and marked kinking of DNA...
  14. ncbi Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme
    Y Pommier
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892 4255, USA
    Biochim Biophys Acta 1400:83-105. 1998
    ..Because of the importance of topoisomerase I as a chemotherapeutic target, we review the mechanisms of action of camptothecins and the other topoisomerase I inhibitors identified to date...
  15. ncbi Crystal structure of an IHF-DNA complex: a protein-induced DNA U-turn
    P A Rice
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 87:1295-306. 1996
    ..One such readout involves a six-base A tract, providing evidence for the importance of a narrow minor groove...
  16. ncbi The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites
    John N Lisgarten
    Institut de Biologia Molecular de Barcelona, C S I C, Jordi Girona 18, 08034 Barcelona, Spain
    Nat Struct Biol 9:57-60. 2002
    ..The crystal structure of this antimalarial drug-DNA complex provides evidence for the first nonalternating intercalation and, as such, provides a basis for the design of new anticancer or antimalarial drugs...
  17. ncbi On the molecular mechanism of drug intercalation into DNA: a simulation study of the intercalation pathway, free energy, and DNA structural changes
    Arnab Mukherjee
    Departement de Chimie, CNRS UMR 8640 PASTEUR, Ecole Normale Superieure, 24 RueLhomond, 75231 Cedex 05, France
    J Am Chem Soc 130:9747-55. 2008
    ..4 kcal/mol. The results point to a mechanism in which the drug first binds to the minor groove and then intercalates into the DNA in an activated process, which is found to be in general agreement with experimental kinetic results...
  18. ncbi DNA-binding of semirigid binuclear ruthenium complex delta,delta-[mu-(11,11'-bidppz)(phen)(4)ru(2)](4+): extremely slow intercalation kinetics
    L Marcus Wilhelmsson
    Department of Physical Chemistry, Chalmers University of Technology, S 41296 Gothenburg, Sweden
    J Am Chem Soc 124:12092-3. 2002
    ..Also, their unique optical and photophysical properties could make such complexes, either alone or scaffolded by DNA structures, of interest for the development of nanometer-sized molecular optoelectronic devices...
  19. ncbi Natural product DNA major groove binders
    Paris L Hamilton
    Department of Chemistry, Clemson University, Clemson, SC 29634, USA
    Nat Prod Rep 29:134-43. 2012
    ..Finally, recent reports of non-covalent major groove binding with carbohydrates, aminoglycosides in particular, have revealed them as promising leads for DNA major groove binding probes or drugs...
  20. ncbi Cytotoxicity and cellular impact of dinuclear organoiridium DNA intercalators and nucleases with long rigid bridging ligands
    Mhd Ali Nazif
    Fakultät für Chemie und Biochemie, Ruhr Universitat Bochum, Bochum, Germany
    Dalton Trans 41:5587-98. 2012
    ..Online studies with a sensor chip system indicated that 5 μM solutions of these complexes invoke a rapid and massive reduction in MCF-7 cell respiration...
  21. ncbi Novel DNA bis-intercalation by MLN944, a potent clinical bisphenazine anticancer drug
    Jixun Dai
    College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA
    J Biol Chem 279:46096-103. 2004
    ..Thus, the exceptional biological activity of MLN944 may be due to its novel DNA binding mode leading to a unique mechanism of action...
  22. ncbi Bisacridines with aromatic linking chains. Synthesis, DNA interaction, and antitumor activity
    Antonio Lorente
    Departamento de Quimica Organica, Universidad de Alcala, Alcala de Henares, 28871 Madrid, Spain
    Bioorg Med Chem 12:4307-12. 2004
    ..Synthesis of a series of bisacridine derivatives containing rigid aromatic linking chains is described. Their DNA interaction and in vitro cytotoxicity against HT-29 human carcinoma cells are reported...
  23. ncbi Molecular recognition of DNA by rigid [N]-polynorbornane-derived bifunctional intercalators: synthesis and evaluation of their binding properties
    Liisa D Van Vliet
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom
    J Med Chem 50:2326-40. 2007
    ..The flexibility of the linker connecting the rings to the scaffold, although less influential, could affect the strength and character of the DNA binding...
  24. pmc DNA base mismatch detection with bulky rhodium intercalators: synthesis and applications
    Brian M Zeglis
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Nat Protoc 2:357-71. 2007
    ..The synthesis of the metallointercalators requires approximately 5-7 d. The mismatch- and SNP-detection experiments each require approximately 3 d...
  25. ncbi The kinetics of YOYO-1 intercalation into single molecules of double-stranded DNA
    Marcel Reuter
    School of Chemistry and COSMIC, The University of Edinburgh, West Mains Road, The King s Buildings, Edinburgh EH9 3JJ, UK
    Biochem Biophys Res Commun 403:225-9. 2010
    ..The kinetics of binding help with interpretation of the behavior of DNA-YOYO-1 complexes when overstretched and establish defined conditions for the preparation of DNA-YOYO-1 complexes...
  26. ncbi Actinomycin D specifically inhibits the interaction between transcription factor Sp1 and its binding site
    M Czyz
    Department of General Chemistry, Institute of Physiology and Biochemistry, Medical University of Lodz, Poland
    Acta Biochim Pol 45:67-73. 1998
    ..The results support the view that DNA-binding drugs displaying high sequence-selectivity can exhibit distinct effects on the interaction between DNA and different DNA-binding proteins...
  27. pmc Intercalation of XR5944 with the estrogen response element is modulated by the tri-nucleotide spacer sequence between half-sites
    Neil Sidell
    Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, United States
    J Steroid Biochem Mol Biol 124:121-7. 2011
    ....
  28. ncbi Solution structure of a quinomycin bisintercalator-DNA complex
    H Chen
    Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons of Columbia University, New York, NY 10032
    J Mol Biol 246:164-79. 1995
    ....
  29. pmc Increasing the analytical sensitivity by oligonucleotides modified with para- and ortho-twisted intercalating nucleic acids--TINA
    Uffe V Schneider
    QuantiBact Inc, Hvidovre, Denmark
    PLoS ONE 6:e20565. 2011
    ..We anticipate that the presented rules for placement of TINA molecules will be broadly applicable in hybridization capture assays and target amplification systems...
  30. ncbi Proton exchange in DNA-luzopeptin and DNA-echinomycin bisintercalation complexes: rates and processes of base-pair opening
    J L Leroy
    Groupe de Biophysique, Ecole Polytechnique, Palaiseau, France
    Biochemistry 31:1407-15. 1992
    ..Thus, the action of the bisintercalating drug may be compared to a vise clamping the inner base pairs. Analysis suggests that base-pair opening may require prior unwinding or bending of the DNA duplex...
  31. ncbi Molecular determinants of topoisomerase I poisoning by lamellarins: comparison with camptothecin and structure-activity relationships
    Esther Marco
    Departamento de Farmacologia, Universidad de Alcala, E 28871 Madrid, Spain
    J Med Chem 48:3796-807. 2005
    ..The deleterious effect of replacing the 20-OH in LMD with a hydrogen was confirmed using a set of thermodynamic integration free energy simulations...
  32. ncbi DNA polymorphism as an origin of adenine-thymine tract length-dependent threading intercalation rate
    Pär Nordell
    Department of Chemical and Biological Engineering, Chalmers University of Technology, SE 41296 Gothenburg, Sweden
    J Am Chem Soc 130:14651-8. 2008
    ..We finally find that mismatches or loops in the oligonucleotide facilitate the threading process, of interest for the development of mismatch-recognizing probes...
  33. pmc A sequence-specific threading tetra-intercalator with an extremely slow dissociation rate constant
    Garen G Holman
    Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA
    Nat Chem 3:875-81. 2011
    ..This is one of the longest non-covalent complex half-lives yet reported and, to the best of our knowledge, the longest for a DNA-binding molecule...
  34. pmc DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient cells to bulky rhodium(III) intercalators
    Jonathan R Hart
    Division of Chemistry and Chemical Engineering, California Institute of Technology Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 103:15359-63. 2006
    ..Targeting DNA mismatches may therefore provide a cell-selective strategy for chemotherapeutic design...
  35. ncbi Tetrakis-acridinyl peptide: a novel fluorometric reagent for nucleic acid analysis based on the fluorescence dequenching upon DNA binding
    Hiroyuki Ueyama
    Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Japan
    Analyst 127:886-8. 2002
    ....
  36. ncbi Determination of binding affinities of triplex forming oligonucleotides using a fluorescent intercalator displacement (FID) assay
    Bryan K S Yeung
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem Lett 13:3801-4. 2003
    ..The binding affinities of several triplex forming oligonucleotides were determined using a fluorescent intercalator displacement (FID) assay...
  37. ncbi Solution structural study of a DNA duplex containing the guanine-N7 adduct formed by a cytotoxic platinum-acridine hybrid agent
    Hemanta Baruah
    Department of Chemistry, Wake Forest University, P O Box 7486 Reynolda Station, Winston Salem, North Carolina 27109, USA
    Biochemistry 44:6059-70. 2005
    ..Instead, intriguing structural similarities are observed for PT-ACRAMTU's monoadduct and the N7 adducts of dual major-groove alkylating/intercalating antitumor agents, such as the pluramycins...
  38. ncbi Design of a sequence-specific DNA bisintercalator
    Eric J Fechter
    Division of Chemistry and Chemical Engineering, 164 30, California Institute of Technology, Pasadena, CA 91125, USA
    Angew Chem Int Ed Engl 43:3591-4. 2004
  39. ncbi Fluorescent intercalator displacement analyses of DNA binding by the peptide-derived natural products netropsin, actinomycin, and bleomycin
    Mark A Lewis
    Department of Chemistry and Chemical Biology, Purdue School of Science, Indiana University Purdue University Indianapolis IUPUI, 402 North Blackford Street, Indianapolis, IN 46202, USA
    Bioorg Med Chem 14:3481-90. 2006
    ....
  40. ncbi An octakis-intercalating molecule
    M M Murr
    Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX 78712, USA
    Bioorg Med Chem 9:1141-8. 2001
    ..Our so-called "octamer" represents, to the best of our knowledge, the first intercalator that binds as an octakis-intercalator, capable of spanning at least 16 base pairs of DNA...
  41. pmc Spermine attenuates the action of the DNA intercalator, actinomycin D, on DNA binding and the inhibition of transcription and DNA replication
    Sheng Yu Wang
    Department of Life Science, National Chung Hsing University, Taichung, Taiwan
    PLoS ONE 7:e47101. 2012
    ..Our findings will be of significant relevance to future developments in combination with cancer therapy by enhancing the anticancer activity of DNA interactors through polyamine depletion...
  42. ncbi DNA binding by analogues of the bifunctional intercalator TANDEM
    Andrew J Hampshire
    School of Biological Sciences, University of Southampton, UK
    Biochemistry 47:7900-6. 2008
    ..By using fragments with different lengths of [(AT) n ], we demonstrate that these ligands bind best to the center of the longer (AT) n tracts...
  43. ncbi Using an aryl phenanthroimidazole moiety as a conjugated flexible intercalator to improve the hybridization efficiency of a triplex-forming oligonucleotide
    Amany M A Osman
    Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK 5230 Odense M, Denmark
    Bioorg Med Chem 16:9937-47. 2008
    ..The required monomers for DNA synthesis using amidite chemistry were obtained by standard deprotection of the hydroxy groups followed by 4,4'-dimethoxytritylation and phosphitylation...
  44. pmc Investigations on DNA intercalation and surface binding by SYBR Green I, its structure determination and methodological implications
    Hubert Zipper
    Laboratory of Biochemistry, Institute for Interfacial Engineering, University of Stuttgart, 70569 Stuttgart, Germany
    Nucleic Acids Res 32:e103. 2004
    ..These structure-property relationships help in the design of methods that use SG, in particular dsDNA quantification in solution and real-time PCR...
  45. ncbi DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action
    Rahul Palchaudhuri
    Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, IL 61801, United States
    Curr Opin Biotechnol 18:497-503. 2007
    ..Together, these assays are powerful tools to determine the mechanism of previously discovered molecules, and will be crucial to the discovery of the next generation of DNA-binding anticancer drugs...
  46. ncbi Genotoxicity of non-covalent interactions: DNA intercalators
    Lynnette R Ferguson
    Auckland Cancer Society Research Centre, Faculty of Medical and Health Science, The University of Auckland, New Zealand
    Mutat Res 623:14-23. 2007
    ..The most extensively studied DNA intercalating agents are acridine and its derivatives, that bind reversibly but non-covalently to DNA...
  47. pmc Insights into finding a mismatch through the structure of a mispaired DNA bound by a rhodium intercalator
    Valérie C Pierre
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 104:429-34. 2007
    ..This structure, illustrating two clearly distinct binding modes for a molecule with DNA, provides a rationale for the interrogation and detection of mismatches...
  48. ncbi Self-structure induction in single stranded poly(A) by small molecules: Studies on DNA intercalators, partial intercalators and groove binding molecules
    Prabal Giri
    Biophysical Chemistry Laboratory, Indian Institute of Chemical Biology, 4, Raja S C Mullick Road, Jadavpur, Kolkata, West Bengal 700032, India
    Arch Biochem Biophys 474:183-92. 2008
    ..Structural and thermodynamic aspects of the interaction leading to self-structure formation are described...
  49. ncbi Intercalating nucleic acids: the influence of linker length and intercalator type on their duplex stabilities
    Ulf B Christensen
    Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Odense, Denmark
    Nucleosides Nucleotides Nucleic Acids 23:207-25. 2004
    ..Six new examples of intercalating nucleic acids were synthesized in order to evaluate the dependence of the length of the linker between oligo and intercalator on the thermal stability of their corresponding duplexes and triplexes...
  50. ncbi NMR structural analysis of a modular threading tetraintercalator bound to DNA
    Jeeyeon Lee
    Department of Chemistry and Biochemistry, The University of Texas, Austin, Texas 78712, USA
    J Am Chem Soc 126:14036-42. 2004
    ..This study represents the first NMR analysis of a threading tetraintercalator and, as such, structurally characterizes a new topology for molecules that bind to relatively long DNA sequences with extensive access to both DNA grooves...
  51. ncbi Alteration of sequence specificity of the type II restriction endonuclease HincII through an indirect readout mechanism
    Hemant K Joshi
    Department of Biochemistry and Molecular Biophysics, University of Arizona, Tucson, Arizona 85721, USA
    J Biol Chem 281:23852-69. 2006
    ..Analysis of these structures and the effect of Ca2+ binding on the protein-DNA interface illuminates the origin of the altered specificity by the mutation Q138F in the HincII enzyme...
  52. ncbi Sequence selectivity and degeneracy of a restriction endonuclease mediated by DNA intercalation
    Nancy C Horton
    Department of Chemistry and Biochemistry, and Interdepartmental Program in Biomolecular Science and Engineering, University of California at Santa Barbara, Santa Barbara, California 93106 9510, USA
    Nat Struct Biol 9:42-7. 2002
    ..Comparison of the HincII and EcoRV cocrystal structures suggests that sequence-dependent differences in base-stacking free energies are a crucial underlying factor mediating protein recognition by indirect readout...
  53. pmc Optimal design of parallel triplex forming oligonucleotides containing Twisted Intercalating Nucleic Acids--TINA
    Uffe V Schneider
    QuantiBact Inc, Department of Clinical Microbiology, Hvidovre Hospital, Kettegaards Alle 30, 2650 Hvidovre, Denmark
    Nucleic Acids Res 38:4394-403. 2010
    ..We predict that TINA stabilized PT will improve the sensitivity and specificity of DNA based clinical diagnostic assays...
  54. pmc Unusual intercalation of acridin-9-ylthiourea into the 5'-GA/TC DNA base step from the minor groove: implications for the covalent DNA adduct profile of a novel platinum-intercalator conjugate
    Hemanta Baruah
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109 7486, USA
    Nucleic Acids Res 31:4138-46. 2003
    ..The unusual tolerance of the GA/TC intercalation site and the pronounced groove specificity of ACRAMTU play a significant role in the molecular recognition between the corresponding platinum conjugate, Pt-ACRAMTU, and DNA...
  55. pmc A pseudocatenane structure formed between DNA and A cyclic bisintercalator
    Yongjun Chu
    Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA
    J Am Chem Soc 131:3499-508. 2009
    ..To the best of our knowledge, this is the first structurally well-characterized pseudocatenane complex between a sequence specific cyclic bisintercalator and intact DNA...
  56. ncbi Peptide bis-intercalator binds DNA via threading mode with sequence specific contacts in the major groove
    V Guelev
    Department of Chemistry and Biochemistry, The University of Texas at Austin, 78722, USA
    Chem Biol 8:415-25. 2001
    ....
  57. ncbi Micelle-sequestered dissociation of cationic DNA-intercalated drugs: unexpected surfactant-induced rate enhancement
    Fredrik Westerlund
    Physical Chemistry Section at the Department of Chemistry and Bioscience, Chalmers University of Technology, SE 41296 Gothenburg, Sweden
    J Am Chem Soc 125:3773-9. 2003
    ..As an alternative, more reliable method, we suggest instead the addition of excess of dummy DNA as an absorbent for dissociated ligand...
  58. pmc The geometry of DNA supercoils modulates topoisomerase-mediated DNA cleavage and enzyme response to anticancer drugs
    A Kathleen McClendon
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 45:3040-50. 2006
    ....
  59. ncbi Structural characterization of a rigidified threading bisintercalator
    Yongjun Chu
    Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA
    J Am Chem Soc 129:1304-11. 2007
    ....
  60. ncbi Bisintercalating threading diacridines: relationships between DNA binding, cytotoxicity, and cell cycle arrest
    Laurence P G Wakelin
    School of Medical Sciences, and the School of Women s and Children s Health, University of New South Wales, Sydney 2052, New South Wales, Australia
    J Med Chem 46:5790-802. 2003
    ..There are no simple relationships between structure, cytotoxicity, and cell cycle arrest, and the origins of this complexity are unclear given that the compounds bind to DNA by a common mechanism...
  61. ncbi Monitoring the DNA binding kinetics of a binuclear ruthenium complex by energy transfer: evidence for slow shuffling
    Fredrik Westerlund
    Department of Chemistry and Bioscience, Chalmers University of Technology, SE 41296 Gothenburg, Sweden
    J Phys Chem B 109:21140-4. 2005
    ..e., whether the ruthenium complex remains threaded (requiring sequential base-pair openings) or if unthreading followed by lateral diffusion within the ionic atmosphere of the DNA and rethreading occurs...
  62. pmc CSI-FID: high throughput label-free detection of DNA binding molecules
    Karl E Hauschild
    Genome Center of Wisconsin, Department of Biochemistry, University of Wisconsin Madison, Madison, WI 53706, USA
    Bioorg Med Chem Lett 19:3779-82. 2009
    ..Analysis of the DNA binding properties of protein- and small molecule-based libraries with CSI-FID will advance the development of genome-anchored molecules for therapeutic purposes...
  63. ncbi Supramolecular DNA recognition
    Michael J Hannon
    School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
    Chem Soc Rev 36:280-95. 2007
    ..Recent discoveries of new binding motifs, and new biological structural and genomic information from bioscience, are affording new opportunities for supramolecular chemistry, where shape, fit and orientation play such an important role...
  64. ncbi Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex
    Bart L Staker
    deCODE BioStructures, 7869 NE Day Road West, Bainbridge Island, Washington 98110, USA
    J Med Chem 48:2336-45. 2005
    ..These new X-ray structures explain how very different molecules can stabilize top1-DNA covalent complexes and will aid the rational design of completely novel structural classes of anticancer drugs...
  65. ncbi The search of DNA-intercalators as antitumoral drugs: what it worked and what did not work
    R Martinez
    Instituto de Quimica, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, Coyoacan 04510, Mexico, D F Mexico
    Curr Med Chem 12:127-51. 2005
    ....
  66. ncbi Putative identification of functional interactions between DNA intercalating agents and topoisomerase II using the V79 in vitro micronucleus assay
    Ronald D Snyder
    DuPont Pharmaceuticals Company, Stine Haskell Research Center, P O Box 50, H1 1710, Newark, DE 19714, USA
    Mutat Res 503:21-35. 2002
    ..It is shown that intercalating agents may be catalytic topo II inhibitors (e.g...
  67. ncbi Acridinecarboxamide topoisomerase poisons: structural and kinetic studies of the DNA complexes of 5-substituted 9-amino-(N-(2-dimethylamino)ethyl)acridine-4-carboxamides
    A Adams
    Department of Biochemistry, University of Sydney, New South Wales, Australia
    Mol Pharmacol 58:649-58. 2000
    ....
  68. ncbi Intercalators as anticancer drugs
    M F Brana
    Departamento de Quimica Organica y Farmaceutica, Facultad de Ciencias Experimentales y de la Salud Monteprincipe Boadilla del Monte, 28668 Madrid, Spain
    Curr Pharm Des 7:1745-80. 2001
    ..b>Intercalating agents share common structural features such as the presence of planar polyaromatic systems which bind by ..
  69. ncbi Noncovalent interactions with DNA: an overview
    Lucjan Strekowski
    Department of Chemistry, Georgia State University, Atlanta, GA 30302 4098, United States
    Mutat Res 623:3-13. 2007
    ..The binding mode with the most favorable free energy for complex formation depends on the DNA sequence and structural features of the bound ligand...
  70. ncbi Thiazole orange as the fluorescent intercalator in a high resolution fid assay for determining DNA binding affinity and sequence selectivity of small molecules
    D L Boger
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem 9:2511-8. 2001
    ..Utilizing a library of hairpin deoxyoligonucleotides containing all possible four base-pair sequences, the method provides a high resolution profile of the DNA binding properties of small molecules in a high throughput format...
  71. ncbi Structural characterisation of bisintercalation in higher-order DNA at a junction-like quadruplex
    Susana C M Teixeira
    School of Chemistry, The University of Reading, Whiteknights, Berkshire, RG6 6AD, Reading, UK
    J Mol Biol 323:167-71. 2002
    ..This higher-order DNA structure provides insight into an unexpected property of bisintercalating threading agents, and suggests the idea of targeting such compounds specifically at four-way DNA junctions...
  72. ncbi Site-selective reactions of imperfectly matched DNA with small chemical molecules: applications in mutation detection
    Chinh T Bui
    Genomic Disorders Research Centre, The University of Melbourne, 7th Floor, Daly Wing, 35 Victoria Parade, Fitzroy, VIC 3065, Melbourne, Australia
    Bioorg Chem 30:216-32. 2002
    ....
  73. ncbi DNA intercalators differentially affect chromatin structure and DNA replication in Xenopus egg extract
    Asmita Kumar
    Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS, USA
    Anticancer Drugs 15:633-9. 2004
    ..This system may prove useful for large scale screening of DNA-interacting chemotherapeutic compounds in a cellular milieu...
  74. ncbi Small molecule intercalation with double stranded DNA: implications for normal gene regulation and for predicting the biological efficacy and genotoxicity of drugs and other chemicals
    Lawrence B Hendry
    Accelerated Pharmaceuticals Inc, Augusta, GA, United States
    Mutat Res 623:53-71. 2007
    ..If double stranded DNA is proven to be the ultimate target of genomic drug action, intercalation will emerge as a cornerstone of the future discovery of safe and effective pharmaceuticals...
  75. ncbi Structure of 9-amino-[N-(2-dimethylamino)propyl]acridine-4-carboxamide bound to d(CGTACG)(2): a comparison of structures of d(CGTACG)(2) complexed with intercalatorsin the presence of cobalt
    Adrienne Adams
    School of Molecular and Microbial Biosciences, University of Sydney, NSW 2006, Australia
    Acta Crystallogr D Biol Crystallogr 60:823-8. 2004
    ..Given the nature of the ligands found in these complexes, the relevance of the quadruplex structure to the biological activity of those agents, known to be topoisomerase poisons, is questioned...
  76. pmc Molecular mechanisms and kinetics between DNA and DNA binding ligands
    Andy Sischka
    Experimental Biophysics and Applied Nanosciences, Department of Physics, Bielefeld University, 33615 Bielefeld, Germany
    Biophys J 88:404-11. 2005
    ..These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively...
  77. ncbi Tuning the DNA reactivity of cis-platinum: conjugation to a mismatch-specific metallointercalator
    Anne Petitjean
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    J Am Chem Soc 126:14728-9. 2004
    ..Thus, the presence of a permanent link to a site-specific intercalator is able to tune the reactivity of the cis-platinum analogue...
  78. pmc A novel form of intercalation involving four DNA duplexes in an acridine-4-carboxamide complex of d(CGTACG)(2)
    A Adams
    Department of Biochemistry, University of Sydney, NSW 2006, Australia, Auckland Cancer Society Research Centre, Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand
    Nucleic Acids Res 28:4244-53. 2000
    ..with respect to the effects of packing forces on DNA crystal structure, and the potential effects of intercalating agents on biochemical processes involving DNA quadruplexes and strand exchanges...
  79. pmc A new bisintercalating anthracycline with picomolar DNA binding affinity
    Jose Portugal
    Instituto de Biologia Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Josep Samitier, 1 5, E 08028, Barcelona, Spain
    J Med Chem 48:8209-19. 2005
    ..These studies, together with an analysis of the cell-cycle traverse in the presence of WP762, suggest that in these cells the new drug is more cytotoxic than the structurally related WP631...
  80. ncbi Anticancer activity of the lanthanum compound [tris(1,10-phenanthroline)lanthanum(III)]trithiocyanate (KP772; FFC24)
    Petra Heffeter
    Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Borschkegasse 8a, 1090 Vienna, Austria
    Biochem Pharmacol 71:426-40. 2006
    ..Together, these data suggest further development of KP772 as a new anticancer metal-drug...
  81. ncbi Physical nature of ethidium and proflavine interactions with nucleic acid bases in the intercalation plane
    Karol M Langner
    Wroclaw University of Technology, Wyb Wyspianskiego 27, 50 370 Wroclaw, Poland
    J Phys Chem B 110:9720-7. 2006
    ....
  82. ncbi Capillary electrophoresis of double-stranded DNA fragments using a new fluorescence intercalating dye EvaGreen
    Fuming Sang
    College of Chemistry and Chemical Engineering, Shanghai Jiaotong University, Shanghai, P R China
    J Sep Sci 29:1275-80. 2006
    ..45-7.59% for peak area within the same day, 1.35-1.63% for migration time and 6.72-12.05% for peak area for three days. Our data demonstrated that EvaGreen is well suited for the dsDNA analysis by CE with LIF detection...
  83. pmc Characterization of the bisintercalative DNA binding mode of a bifunctional platinum-acridine agent
    Jayati Roy Choudhury
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109 7486, USA
    Nucleic Acids Res 33:5622-32. 2005
    ....
  84. ncbi Metallobleomycin-mediated cleavage of DNA not involving a threading-intercalation mechanism
    A T Abraham
    Contribution from the Departments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA
    J Am Chem Soc 123:5167-75. 2001
    ..blm a(5), co(iii).blm a(5), or cu(i).blm a(5)...
  85. pmc Intercalator conjugates of pyrimidine locked nucleic acid-modified triplex-forming oligonucleotides: improving DNA binding properties and reaching cellular activities
    Erika Brunet
    Laboratoire de Biophysique, Museum national d histoire naturelle, USM 0503, CNRS UMR 5153, INSERM U 565 43 rue Cuvier, 75005 Paris, France
    Nucleic Acids Res 33:4223-34. 2005
    ..1 microM for acridine-conjugated TFO/LNA (or approximately 2 microM for the unconjugated TFO/LNA) whereas the corresponding phosphodiester TFO was inactive, and it was demonstrated to be triplex-mediated...
  86. pmc Cyanine dyes as intercalating agents: kinetic and thermodynamic studies on the DNA/Cyan40 and DNA/CCyan2 systems
    Tarita Biver
    Dipartimento di Chimica e Chimica Industriale, Universita di Pisa, Pisa, Italy
    Biophys J 89:374-83. 2005
    ..Absorption spectra reveal that both dyes tend to self-aggregate; the kinetics of CCyan2 self-aggregation is studied by T-jump relaxation and the results are interpreted in terms of dimer formation...
  87. ncbi Discriminating small molecule DNA binding modes by single molecule force spectroscopy
    Rupert Krautbauer
    Lehrstuhl für Angewandte Physik and CeNS, Luwig Maximilians Universität, Munich, Germany
    FEBS Lett 510:154-8. 2002
    ..The minor groove binder berenil, the crosslinker cisplatin and the intercalator ethidium bromide are compared...
  88. ncbi Quantifying force-dependent and zero-force DNA intercalation by single-molecule stretching
    Ioana D Vladescu
    Department of Physics, Northeastern University, Boston, Massachusetts 02115, USA
    Nat Methods 4:517-22. 2007
    ..The results showed that the applied force partially relieves normal intercalation constraints. We also characterized the flexibility of intercalator-saturated dsDNA for the first time...
  89. ncbi Anthracycline-dependent heat-induced transition from positive to negative supercoiled DNA
    Viktor Viglasky
    Institute of Chemistry, Department of Biochemistry, Faculty of Sciences, P J Safarik University, Kosice, Slovakia
    Electrophoresis 24:1703-11. 2003
    ..In spite of their different chemical structures and intercalation mode, all intercalating agents show similar effects on the conformational stability of supercoiled DNA...
  90. ncbi Molecular dynamics simulations and thermodynamics analysis of DNA-drug complexes. Minor groove binding between 4',6-diamidino-2-phenylindole and DNA duplexes in solution
    Nad a Spacková
    Institute of Biophysics, Academy of Sciences of the Czech Republic, and National Center for Biomolecular Research, Kralovopolska 135, 612 65 Brno, Czech Republic
    J Am Chem Soc 125:1759-69. 2003
    ....
  91. ncbi Transcription factors as targets for DNA-interacting drugs
    Marek Gniazdowski
    Department of Medicinal Chemistry, Institute of Physiology and Biochemistry, Medical University of Lodz, Poland
    Curr Med Chem 10:909-24. 2003
    ..In this review, we have summarized recent advances which have been made towards understanding the above mechanisms by which small molecules interfere with the function of transcription factors...
  92. ncbi Comparison of SYBR Green I nucleic acid gel stain mutagenicity and ethidium bromide mutagenicity in the Salmonella/mammalian microsome reverse mutation assay (Ames test)
    V L Singer
    Molecular Probes, 4849 Pitchford Avenue, Eugene, OR, USA
    Mutat Res 439:37-47. 1999
    ..These results suggest that SYBR Green I stain may not intercalate, and if it does, that its presence does not give rise to point mutations at a high frequency...
  93. ncbi Effect of DNA-binding drugs on early growth response factor-1 and TATA box-binding protein complex formation with the herpes simplex virus latency promoter
    S Y Chiang
    Experimental Therapeutics Department, Roswell Park Cancer Institute, Buffalo, New York 14263, USA
    J Biol Chem 271:23999-4004. 1996
    ..TFIIA.DNA complex and restored the EGR1.DNA complex. We conclude that the binding motif and sequence preference of DNA-interactive drugs are manifested in their ability to inhibit the transcription factor-DNA complexes...
  94. pmc Controlling nucleic acid secondary structure by intercalation: effects of DNA strand length on coralyne-driven duplex disproportionation
    Swapan S Jain
    School of Chemistry and Biochemistry, Parker H Petit Institute of Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332 0400, USA
    Nucleic Acids Res 31:4608-15. 2003
    ..Together these observations indicate that at least one secondary structure in our nucleic acid system [i.e. duplex, triplex or (dA)n self-structure] binds coralyne in a length-dependent manner...
  95. pmc Identification of binding mechanisms in single molecule-DNA complexes
    Rainer Eckel
    Experimental Biophysics and Applied Nanosciences, Faculty of Physics, Bielefeld University, 33615 Bielefeld, Germany
    Biophys J 85:1968-73. 2003
    ..These findings lead to the conclusion that atomic force microscope force spectroscopy can be regarded as a single molecule biosensor and is a potent tool for the characterization of binding motives of small ligands to DNA...
  96. ncbi Synthesis and antitumor activity of novel amsacrine analogs: the critical role of the acridine moiety in determining their biological activity
    Adriana Chilin
    Department of Pharmaceutical Sciences, University of Padova, Via Marzolo, 5, 35131 Padova, Italy
    Bioorg Med Chem 17:523-9. 2009
    ....
  97. ncbi Transition on the entropic elasticity of DNA induced by intercalating molecules
    M S Rocha
    Departamento de Fisica, ICEx, Universidade Federal de Minas Gerais, Caixa Postal 702, Belo Horizonte, CEP 31270 901 Minas Gerais, Brazil
    J Chem Phys 127:105108. 2007
    ..The neighbor exclusion model fits to our results for the total drug concentration as a function of the relative increase of the contour length...
  98. ncbi Tight binding of the antitumor drug ditercalinium to quadruplex DNA
    Carolina Carrasco
    INSERM U 524 et Laboratoire de Pharmacologie, Antitumorale du Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Lille, France
    Chembiochem 3:1235-41. 2002
    ..The newly discovered preferential binding of ditercalinium to the antiparallel quadruplex sequence d(AG(3)[T(2)AG(3)](3)) provides new perspectives for the design of drugs that can bind to human telomeres...
  99. pmc Direct observation of the reversible unwinding of a single DNA molecule caused by the intercalation of ethidium bromide
    Masahito Hayashi
    The Tokyo Metropolitan Institute of Medical Science, Bunkyo ku, Tokyo, Japan
    Nucleic Acids Res 35:e125. 2007
    ..The association constant of EtBr and dsDNA (1.9 (+/-0.1) x 10(5) M(-1)) was consistent with that of previous results. Our system is useful to investigate the twisting of a single dsDNA interacting with various chemicals and biomolecules...
  100. pmc Insertion of a bulky rhodium complex into a DNA cytosine-cytosine mismatch: an NMR solution study
    Christine Cordier
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    J Am Chem Soc 129:12287-95. 2007
    ..These results corroborate those obtained crystallographically and, importantly, provide structural evidence for this specific insertion mode in solution...
  101. ncbi Effects of minor groove binding drugs on the interaction of TATA box binding protein and TFIIA with DNA
    S Y Chiang
    Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263
    Biochemistry 33:7033-40. 1994
    ....

Research Grants42

  1. DNA Methyltransferase Inhibition by Intercalating Agents
    Keith D Robertson; Fiscal Year: 2010
    ..hypothesis we plan to test in this application is that inhibition of DNA methyltransferases (DNMTs) by DNA intercalating agents leads to alterations in genomic DNA methylation patterns and contributes directly to intercalator-mediated ..
  2. SIDEROPHORES, ANALOGS AND BIOCONJUGATES
    Marvin Miller; Fiscal Year: 1999
    ..f) Syntheses of specific desferal-DNA intercalating agents will lead to development of new antimalarial agents...
  3. RNA-SPECIFIC LIGANDS: AN APPROACH TO NEW ANTIVIRALS
    PETER BEAL; Fiscal Year: 2003
    ..In addition, these new compounds would have the potential to be developed into therapeutics for viral and bacterial infections. ..
  4. REACTIVE INTERMEDIATES OF CARCINOGENESIS OF PAHS
    KENNETH LAALI; Fiscal Year: 2004
    ..Nitro-PAHs will be used to synthesize novel DNA-intercalating agents. A unique feature of this work is that reactive intermediates are examined directly...
  5. SPECIFICITY OF INTERCALATOR DIRECTED GENOTOXICITY
    Russell Anderson; Fiscal Year: 1993
    The broad goal of the proposed studies is to define mechanisms by which intercalating agents mediate mutation and lethality at the DNA level...
  6. THERMODYNAMICS OF DNA CONFORMATION AND INTERACTIONS
    LUIS MARKY; Fiscal Year: 1999
    ..structures) containing bulges and mismatches and to characterize hydration effects from interactions with intercalating agents. Complete thermodynamics profiles (deltaG, deltaH, delta S and deltaV) will be obtained...
  7. 13C AND OTHER NUCLEI NMR OF DNA AND DNA INTERACTIONS
    GEORGE LEVY; Fiscal Year: 1980
    ..Small molecules chosen for study include intercalating agents (proflavine, ethidium, quinacrine, actinomycin D; a steroid diamine (dipyrandium): alkylating agents ..
  8. DNA DAMAGE AND REPAIR BY ANTITUMOR AGENTS
    WARREN ROSS; Fiscal Year: 1990
    ..work of others, it is now clear that topolsomerase II is the major intracellular target for a variety of intercalating agents and epipodophyllotoxins...
  9. TARGETABLE FORMULATIONS FOR NOVEL ANTI-CANCER AGENTS
    Keelung Hong; Fiscal Year: 2001
    We propose to develop targetable formulations of promising anti-cancer agents (DNA-intercalating agents, Cucurbitacin derivatives, and Swainsonine) which have undergone evaluation by NCI's in vitro anticancer screening and are considered ..
  10. Anti-Inflammatory Bioconjugates
    Benjamin Bowen; Fiscal Year: 2008
    ....
  11. PHENYLACETATE--NOVEL THERAPEUTIC USES IN BREAST CANCER
    Neil Sidell; Fiscal Year: 2005
    ..Taken together, the information gained from these studies will provide a basic framework for the rationale use of PA analogs or similar acting compounds in the clinic. ..
  12. Fostriecin and Related Protein Phosphatase Inhibitors
    Dale Boger; Fiscal Year: 2005
    ....
  13. DOES PKU PROTECT AGAINST CANCER?
    Neil Sidell; Fiscal Year: 2003
    ....
  14. Histone Deacetylase Inhibitors as Therapeutics for Friedreich's ataxia
    JOEL GOTTESFELD; Fiscal Year: 2007
    ..We are developing small molecules to reverse this effect, with the hope that these molecules may be therapeutic for FRDA. [unreadable] [unreadable] [unreadable]..
  15. ULTRAVIOLET LIGHT INDUCED PHENOMENA IN BIOMEMBRANES
    IRENE KOCHEVAR; Fiscal Year: 2006
    ..Human keratinocytes and fibroblasts will be supplemented with 7-DHC, and UVA-induced production of PGE2 and IL-lcc will measured. ..
  16. FUNCTIONAL AND MECHANISTIC STUDIES OF DNA TOPOISOMERASES
    Leroy Liu; Fiscal Year: 2001
    ..We will also determine which TOP2 isoform is responsible for HMW DNA fragmentation during apoptotic cell death. ..
  17. SYNTHETIC GENE CARRIERS TO TREAT CYSTIC FIBROSIS
    FRANCIS SZOKA; Fiscal Year: 2001
    ..abstract_text> ..
  18. Labeled Thymidine -- Development as A PET Imaging Agent
    Anthony Shields; Fiscal Year: 2008
    ..Our ultimate goal is to demonstrate that this approach is useful in evaluating both experimental and routine clinical treatment. ..
  19. Pharmacology of Targeted Therapy to Brain Tumors
    FRANCIS SZOKA; Fiscal Year: 2008
    ..These results will provide a rationale for targeted therapies for human brain tumors. ..
  20. Polyamide-Chl inhibition of cancer cell proliferation
    JOEL GOTTESFELD; Fiscal Year: 2009
    ..The mechanism of inhibition of transcription by polyamides will be assessed both in vitro, in cell culture and in animal models...
  21. Redox-Active Agents for Pancreatic Cancer
    Robert Dorr; Fiscal Year: 2009
    ..The underlying clinical trial is underway and has already produced objective evidence of efficacy for this drug combination. ..
  22. New Hydropathy-Based computer Tools for Drug Discovery
    GLEN KELLOGG; Fiscal Year: 2009
    ..Specific collaborative arrangements are in place to apply these tools to a range of current drug discovery problems. ..
  23. Small Molecular Therapeutics for Friedreich's Ataxia
    Joel M Gottesfeld; Fiscal Year: 2010
    ..These repeats inactivate the gene, and we have developed small molecules that reverse this inactivation by targeting the GAA repeats. ..
  24. Biocompatible Dendritic Polymers for in vivo Applications
    FRANCIS SZOKA; Fiscal Year: 2009
    ..Completion of this research will enable a variety of substantially improved targeted therapies and diagnostic imaging applications that can be successfully applied to treat humans with cancer. ..
  25. Role of E2F2 in eugenol-induced melanoma growth inhibit*
    Rita Ghosh; Fiscal Year: 2006
    ..This proposal addresses this very core of cancer chemoprevention that aims to reduce the national burden of high cost of treatment and loss of productive life. ..
  26. Small molecule therapeutics for Friedreich's ataxia
    JOEL GOTTESFELD; Fiscal Year: 2005
    ..The effects of polyamides on cellular frataxin protein will be determined by western blotting, and the genome-wide effects of polyamide treatment will be assessed by DNA microarray analysis. ..
  27. Biocompatible Dendritic Polymers : In Vivo Applications
    FRANCIS SZOKA; Fiscal Year: 2002
    ..abstract_text> ..
  28. PET IMAGING OF DRUG KINETICS AND PATHWAYS
    Anthony Shields; Fiscal Year: 2002
    ..Our proposed study of [F-18]FAU with PET will provide information on the biodistribution of this new therapeutic agent and may provide a way to image tumor TS activity and proliferation. ..
  29. MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
    IRENE KOCHEVAR; Fiscal Year: 2003
    ..Elastase inhibitors will also be employed in vivo. In vitro experiments using human dermal fibroblasts grown in contracted collagen gels or skin equivalents will be used to define mechanisms for the phenomena observed in vivo. ..
  30. ORGANOMETALLIC SYNTHESES OF BIOACTIVE COMPOUNDS
    LOUIS HEGEDUS; Fiscal Year: 2003
    ..abstract_text> ..
  31. Topoisomerase I-directed Anticancer Drugs
    Leroy Liu; Fiscal Year: 2004
    ..abstract_text> ..
  32. INHIBITION OF HIV GENE TRANSCRIPTION BY SMALL MOLECULES
    JOEL GOTTESFELD; Fiscal Year: 2004
    ..Given our success in inhibition of virus replication in cell culture, we propose collaborative preclinical studies with the Mosier laboratory to determine the effectiveness of polyamides in the human PBL-SCID mouse model. ..
  33. SMALL MOLECULE REGULATION OF BREAST CANCER EXPRESSION
    JOEL GOTTESFELD; Fiscal Year: 2002
    ..Toxicity of the polyamides will be assessed in cell-based assays and non-specific effects of the polyamides on genome-wide gene expression will be monitored using high density DNA array/hybridization methodology. ..
  34. Specificity of Protein-DNA/RNA Interactions
    JOEL GOTTESFELD; Fiscal Year: 2004
    ..Thus, understanding the basis for nucleic acid recognition and dimerization specificity may provide the necessary background for development of the novel therapeutic approaches. ..
  35. Oral Delivery of DNA Vaccines
    FRANK ORSON; Fiscal Year: 2003
    ....
  36. SICKLE RBC, INTERMITTENT HYPOXIA AND VASCULAR PATHOLOGY
    FRANS KUYPERS; Fiscal Year: 2003
    ..Together, our results may indicate novel treatment regiments in the management of SCD. ..
  37. Molecular recognition studies of human PB1 bromodomains
    Martin Thompson; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  38. BIACORE 3000
    DAVID DIGNAM; Fiscal Year: 2003
    ..The availability of this type of state of the art instrumentation will aid NIH supported investigators significantly in pursuing the aims of their research projects ..
  39. Antitumor Drugs that Bind the DNA Minor Groove
    TODD ECKDAHL; Fiscal Year: 2003
    ..abstract_text> ..