Ulrich Bierbach

Summary

Affiliation: Wake Forest University
Country: USA

Publications

  1. ncbi request reprint Adenine-N3 in the DNA minor groove - an emerging target for platinum containing anticancer pharmacophores
    Rajsekhar Guddneppanavar
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Anticancer Agents Med Chem 7:125-38. 2007
  2. pmc A non-cross-linking platinum-acridine agent with potent activity in non-small-cell lung cancer
    Zhidong Ma
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 51:7574-80. 2008
  3. ncbi request reprint Synthesis, biological activity, and DNA-damage profile of platinum-threading intercalator conjugates designed to target adenine
    Rajsekhar Guddneppanavar
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 49:3204-14. 2006
  4. pmc Gold(I) analogues of a platinum-acridine antitumor agent are only moderately cytotoxic but show potent activity against Mycobacterium tuberculosis
    Lauren C Eiter
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 52:6519-22. 2009
  5. ncbi request reprint Effect of the diamine nonleaving group in platinum-acridinylthiourea conjugates on DNA damage and cytotoxicity
    Rajsekhar Guddneppanavar
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 50:2259-63. 2007
  6. pmc Effect of linkage geometry on biological activity in thiourea- and guanidine-substituted acridines and platinum-acridines
    Zhidong Ma
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Bioorg Med Chem Lett 18:3799-801. 2008
  7. ncbi request reprint 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
  8. doi request reprint DNA metalating-intercalating hybrid agents for the treatment of chemoresistant cancers
    Jimmy Suryadi
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    Chemistry 18:12926-34. 2012
  9. pmc Tuning the DNA conformational perturbations induced by cytotoxic platinum-acridine bisintercalators: effect of metal cis/trans isomerism and DNA threading groups
    Jayati Roy Choudhury
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    J Med Chem 51:3069-72. 2008
  10. ncbi request reprint DNA minor groove adducts formed by a platinum-acridine conjugate inhibit association of tata-binding protein with its cognate sequence
    Michael E Budiman
    Department of Chemistry, Wake Forest University, P O Box 7486, Reynolda Station, Winston Salem, North Carolina 27109, USA
    Biochemistry 44:11262-8. 2005

Research Grants

  1. Novel DNA-metalating Hybrid Anticancer Agents
    Ulrich Bierbach; Fiscal Year: 2006
  2. Novel DNA-metalating Hybrid Anticancer Agents
    Ulrich Bierbach; Fiscal Year: 2010

Collaborators

  • Rebecca W Alexander
  • Gregory L Kucera
  • Hemanta Baruah
  • Cynthia S Day
  • Gilda Saluta
  • Lu Rao
  • Rajsekhar Guddneppanavar
  • Zhidong Ma
  • Jayati Roy Choudhury
  • Song Ding
  • Xin Qiao
  • Colin G Barry
  • Marcus W Wright
  • Jimmy Suryadi
  • Suzanne M Hess
  • Michael E Budiman
  • Alexander R Kheradi
  • Leigh A Graham
  • Margaret C Ackley
  • Tiffany K West
  • Todd M Augustus
  • Lauren C Eiter
  • Yan Ma
  • Amanda M Mounce
  • Jennifer M Brow
  • Glen S Marrs
  • Keith E Levine
  • Amal S Essader
  • Alexandra E Zeitany
  • Joshua D Dworkin
  • William E Nell
  • Nathan W Hall
  • Bartlett D Steen
  • Alyssa K Tomsey
  • Russel C Sequeira
  • Joel G Anderson
  • Michael C Farmer
  • Susan J Berners-Price
  • Beth Erin Springer
  • Joel Anderson
  • Susanne M Monnier
  • Christopher L Rector
  • Elizabeth C Turney
  • Cynthia R Pleatman

Detail Information

Publications39

  1. ncbi request reprint Adenine-N3 in the DNA minor groove - an emerging target for platinum containing anticancer pharmacophores
    Rajsekhar Guddneppanavar
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Anticancer Agents Med Chem 7:125-38. 2007
    ....
  2. pmc A non-cross-linking platinum-acridine agent with potent activity in non-small-cell lung cancer
    Zhidong Ma
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 51:7574-80. 2008
    ..5 mg/kg. Compound 4b is the first non-cross-linking platinum agent endowed with promising activity in NSCLC...
  3. ncbi request reprint Synthesis, biological activity, and DNA-damage profile of platinum-threading intercalator conjugates designed to target adenine
    Rajsekhar Guddneppanavar
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 49:3204-14. 2006
    ..One of the conjugates showed significantly higher levels of binding to A-containing sites than conjugate 2 (35 +/- 3% vs 24 +/- 3%). Possible structure-activity relationships are discussed...
  4. pmc Gold(I) analogues of a platinum-acridine antitumor agent are only moderately cytotoxic but show potent activity against Mycobacterium tuberculosis
    Lauren C Eiter
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 52:6519-22. 2009
    ..Instead, several gold analogues show submicromolar and selective antimicrobial activity against Mycobacterium tuberculosis...
  5. ncbi request reprint Effect of the diamine nonleaving group in platinum-acridinylthiourea conjugates on DNA damage and cytotoxicity
    Rajsekhar Guddneppanavar
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 50:2259-63. 2007
    ..Conjugate 3 showed the strongest non-cisplatin-type DNA damage in polymerase stop assays and superior cell kill efficacy in H460 lung cancer (IC50 = 70 nM)...
  6. pmc Effect of linkage geometry on biological activity in thiourea- and guanidine-substituted acridines and platinum-acridines
    Zhidong Ma
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Bioorg Med Chem Lett 18:3799-801. 2008
    ..Conjugate 4' represents a new chemotype with potential applications in the treatment of chemoresistant tumors...
  7. ncbi request reprint 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...
  8. doi request reprint DNA metalating-intercalating hybrid agents for the treatment of chemoresistant cancers
    Jimmy Suryadi
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    Chemistry 18:12926-34. 2012
    ..This article summarizes milestones in the development of these agents and reviews critical key concepts that have guided their design and that of related compounds...
  9. pmc Tuning the DNA conformational perturbations induced by cytotoxic platinum-acridine bisintercalators: effect of metal cis/trans isomerism and DNA threading groups
    Jayati Roy Choudhury
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    J Med Chem 51:3069-72. 2008
    ..Circular dichroism spectra and chemical footprinting experiments suggest that 4, the most active derivative in HL-60 cells, produces a structurally severely perturbed DNA with features of a Hoogsteen base-paired biopolymer...
  10. ncbi request reprint DNA minor groove adducts formed by a platinum-acridine conjugate inhibit association of tata-binding protein with its cognate sequence
    Michael E Budiman
    Department of Chemistry, Wake Forest University, P O Box 7486, Reynolda Station, Winston Salem, North Carolina 27109, USA
    Biochemistry 44:11262-8. 2005
    ..PT-ACRAMTU appears to be the first platinum-based drug capable of targeting DNA sequences critical for transcription initiation. The biological consequences of PT-ACRAMTU's minor groove adducts are discussed...
  11. ncbi request reprint Duplex-promoted platination of adenine-N3 in the minor groove of DNA: challenging a longstanding bioinorganic paradigm
    Colin G Barry
    Department of Chemistry, Wake Forest University, PO Box 7486, Reynolda Station, Winston Salem, North Carolina 27109, USA
    J Am Chem Soc 127:1160-9. 2005
    ..The biological consequences and potential therapeutic applications of the unique base and groove recognition of PT-ACRAMTU are discussed...
  12. pmc Design of a platinum-acridine-endoxifen conjugate targeted at hormone-dependent breast cancer
    Song Ding
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    Chem Commun (Camb) 49:2415-7. 2013
    ....
  13. pmc Using a build-and-click approach for producing structural and functional diversity in DNA-targeted hybrid anticancer agents
    Song Ding
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 55:10198-203. 2012
    ..The new prescreening methodology proves to be a powerful tool for establishing structure-activity relationships and for identifying target compounds...
  14. pmc Analysis of the DNA damage produced by a platinum-acridine antitumor agent and its effects in NCI-H460 lung cancer cells
    Xin Qiao
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    Metallomics 4:645-52. 2012
    ..Possible implications of these findings for the mechanism of action of compound 1 and the agent's potential to overcome tumor resistance to cisplatin are discussed...
  15. ncbi request reprint Structure-activity relationships in platinum-acridinylthiourea conjugates: effect of the thiourea nonleaving group on drug stability, nucleobase affinity, and in vitro cytotoxicity
    Margaret C Ackley
    Department of Chemistry, Wake Forest University, P O Box 7486 Reynolda Station, Winston Salem, NC 27109, USA
    J Biol Inorg Chem 9:453-61. 2004
    ..Possible consequences of the reported structural modifications for the mechanism of action of these agents are discussed...
  16. pmc Rates of intercalator-driven platination of DNA determined by a restriction enzyme cleavage inhibition assay
    Jayati Roy Choudhury
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    J Biol Inorg Chem 16:373-80. 2011
    ..Potential pharmacological advantages of rapid formation of cytotoxic monofunctional adducts over the common purine-purine cross-links are discussed...
  17. pmc Synthesis and biological evaluation of platinum-acridine hybrid agents modified with bipyridine non-leaving groups
    Alexander R Kheradi
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Bioorg Med Chem Lett 19:3423-5. 2009
    ..NMR and mass spectrometry data indicate that bpy accelerates the reaction of platinum with DNA nitrogen, but the resulting adducts are more labile than those formed by the prototype...
  18. ncbi request reprint Platinum-intercalator conjugates: from DNA-targeted cisplatin derivatives to adenine binding complexes as potential modulators of gene regulation
    Hemanta Baruah
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109 7486, USA
    Curr Top Med Chem 4:1537-49. 2004
    ....
  19. ncbi request reprint Unprecedented monofunctional metalation of adenine nucleobase in guanine- and thymine-containing dinucleotide sequences by a cytotoxic platinum-acridine hybrid agent
    Colin G Barry
    Department of Chemistry, Wake Forest University, P O Box 7486 Reynolda Station, Winston Salem, North Carolina 27109, USA
    J Am Chem Soc 125:9629-37. 2003
    ..Possible biological consequences of the unusual adduct profile are discussed...
  20. ncbi request reprint Unique base-step recognition by a platinum-acridinylthiourea conjugate leads to a DNA damage profile complementary to that of the anticancer drug cisplatin
    Michael E Budiman
    Department of Chemistry, Wake Forest University, P O Box 7486 Reynolda Station, Winston Salem, North Carolina 27109, USA
    Biochemistry 43:8560-7. 2004
    ..2003) J. Am. Chem. Soc. 125, 9629-9637]. Possible DNA-binding mechanisms and biological consequences of the unprecedented modification of alternating TA sequences by 2, which occurred at a faster rate than binding to G, are discussed...
  21. ncbi request reprint Bis(acridinylthiourea)platinum(II) complexes: synthesis, DNA affinity, and biological activity in glioblastoma cells
    Todd M Augustus
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Bioorg Med Chem Lett 13:855-8. 2003
    ..A cell viability assay was used to demonstrate that both compounds are capable of mediating cytotoxicity at micromolar concentrations in SNB19 brain tumor cells...
  22. pmc Replacement of a thiourea-S with an amidine-NH donor group in a platinum-acridine antitumor compound reduces the metal's reactivity with cysteine sulfur
    Zhidong Ma
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 52:3424-7. 2009
    ..Possible consequences of the unique target-selective tuning of the substitution chemistry for the pharmacodynamic properties and biological activity of these agents are discussed...
  23. ncbi request reprint Unexpected reactivity of the 9-aminoacridine chromophore in guanidylation reactions
    Zhidong Ma
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Org Chem 72:5387-90. 2007
    ..The newly established reactivities provide efficient pathways to novel cyclic and spirocyclic acridine derivatives...
  24. ncbi request reprint Metal-intercalator-mediated self-association and one-dimensional aggregation in the structure of the excised major DNA adduct of a platinum-acridine agent
    Hemanta Baruah
    Department of Chemistry, Wake Forest University, P O Box 7486, Reynolda Station, Winston Salem, North Carolina 27109, USA
    J Am Chem Soc 126:4492-3. 2004
    ..NMR evidence exists that indicates that the dimeric form persists in neutral aqueous solution. The one-dimensional pi-stack produced by the dimers in the solid state is reminiscent of a coordinative-intercalative DNA binding mode...
  25. 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
    ....
  26. ncbi request reprint Biophysical characterization and molecular modeling of the coordinative-intercalative DNA monoadduct of a platinum-acridinylthiourea agent in a site-specifically modified dodecamer
    Hemanta Baruah
    Department of Chemistry, Wake Forest University, PO Box 7486 Reynolda Station, Winston Salem, NC 27109, USA
    J Biol Inorg Chem 9:335-44. 2004
    ..Differences in the biophysical properties betweenIII* and duplexes containing adducts of the clinical-drug cisplatin are outlined, and possible biological consequences are discussed...
  27. ncbi request reprint Synthesis, structure, and reactivity of monofunctional platinum(II) and palladium(II) complexes containing the sterically hindered ligand 6-(methylpyridin-2-yl)acetate
    Yan Ma
    Department of Chemistry, Wake Forest University, P O Box 7486, Reynolda Station, Winston Salem, NC 27109, United States
    J Inorg Biochem 99:2013-23. 2005
    ..Both the unusual reactivity and the inability to induce cisplatin-like DNA conformational changes are proposed to be responsible for the marginal biological activity of the new complexes...
  28. ncbi request reprint Thermally inert metal ammines as light-inducible DNA-targeted agents. Synthesis, photochemistry, and photobiology of a prototypical rhodium(III)-intercalator conjugate
    Colin G Barry
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    Inorg Chem 41:7159-69. 2002
    ..Acridine 2 alone produced double-strand breaks. The extent of DNA damage observed for 1-3 correlates with the photocytotoxicity of the compounds in human leukemia cells, suggesting that DNA might be the cellular target of these agents...
  29. 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...
  30. pmc Interactions of a platinum-modified perylene derivative with the human telomeric G-quadruplex
    Lu Rao
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Phys Chem B 115:13701-12. 2011
    ..Potential biomedical and biochemical applications of the platinum-perylene technology are discussed...
  31. pmc Probing platinum-adenine-n3 adduct formation with DNA minor-groove binding agents
    Lu Rao
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Chem Res Toxicol 23:1148-50. 2010
    ....
  32. ncbi request reprint Guanine binding of a cytotoxic platinum-acridin-9-ylthiourea conjugate monitored by 1-D 1H and 2-D [1H,15N] NMR spectroscopy: hydrolysis is not the rate-determining step
    Rajsekhar Guddneppanavar
    Department of Chemistry, Wake Forest University, P O Box 7486, Reynolda Station, Winston Salem, NC 27109, USA
    J Inorg Biochem 100:972-9. 2006
    ..The possibility of direct substitution of chloride in 1 by dG-N7 (k(3)) and the implications of the data acquired in this model system for the binding of the conjugate to double-stranded DNA are discussed...
  33. pmc Kinetically favored platination of adenine in the g-rich human telomeric repeat
    Lu Rao
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Am Chem Soc 129:15764-5. 2007
    ....
  34. doi request reprint Using Fluorescent Post-Labeling To Probe the Subcellular Localization of DNA-Targeted Platinum Anticancer Agents
    Song Ding
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109 USA
    Angew Chem Int Ed Engl 52:3350-4. 2013
    ..The platinum-acridine agent was shown to accumulate in the nucleoli of cancer cells (NCI-H460)...
  35. pmc Synthesis, aqueous reactivity, and biological evaluation of carboxylic acid ester-functionalized platinum-acridine hybrid anticancer agents
    Leigh A Graham
    Department of Chemistry, Wake Forest University, Winston Salem, North Carolina 27109, USA
    J Med Chem 55:7817-27. 2012
    ..Potential applications of the chloride-sensitive ester hydrolysis as a self-immolative release mechanism for tumor-selective delivery of platinum-acridines are discussed...
  36. ncbi request reprint Cytotoxic acridinylthiourea and its platinum conjugate produce enzyme-mediated DNA strand breaks
    Jennifer M Brow
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109, USA
    Bioorg Med Chem Lett 12:2953-5. 2002
    ..Assays were based on evaluating DNA cleavage products resulting from incubations of drug-modified DNA in cell-free systems. 2 produces double-strand breaks in the presence of topo II while 1 proved to be a dual topo I/topo II poison...
  37. ncbi request reprint Mechanism of action of non-cisplatin type DNA-targeted platinum anticancer agents: DNA interactions of novel acridinylthioureas and their platinum conjugates
    Hemanta Baruah
    Department of Chemistry, Wake Forest University, Winston Salem, NC 27109 7486, USA
    Biochem Pharmacol 64:191-200. 2002
    ..The difference in DNA binding modes of 4 and 5 is discussed as the ultimate source of the distinctly different biological activities of the conjugates...
  38. ncbi request reprint Platinum-acridinylthiourea conjugates show cell line-specific cytotoxic enhancement in H460 lung carcinoma cells compared to cisplatin
    Suzanne M Hess
    Department of Radiation Oncology, Wake Forest University School of Medicine, Medical Center Blvd, Winston Salem, NC 27157, USA
    Cancer Chemother Pharmacol 56:337-43. 2005
    ..These results suggest that type I/n=2 and type I/n=3 may be promising agents for the treatment of lung cancer and should be pursued in animal models...
  39. ncbi request reprint A non-crosslinking platinum-acridine hybrid agent shows enhanced cytotoxicity compared to clinical BCNU and cisplatin in glioblastoma cells
    Suzanne M Hess
    Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Bioorg Med Chem Lett 15:443-6. 2005
    ..PT-ACRAMTU is more cytotoxic than ACRAMTU (the platinum-free acridine), acts in a time and dose dependent manner, and appears to generate an apoptotic response in both cell lines on the basis of increased caspase-3 activity...

Research Grants6

  1. Novel DNA-metalating Hybrid Anticancer Agents
    Ulrich Bierbach; Fiscal Year: 2006
    ..The results expected from this study will reveal novel concepts of wide importance and interest to the scienific communities involved both in drug discovery and bioinorganic chemistry. ..
  2. Novel DNA-metalating Hybrid Anticancer Agents
    Ulrich Bierbach; Fiscal Year: 2010
    ....