Diploma (Chemistry), 1989, University of Oldenburg, Germany
Ph.D., 1992, University of Oldenburg, Germany (S. Pohl)
Postdoctoral Fellow (German Research Council, DFG), 1992–1993, Leiden University, The Netherlands (J. Reedijk)
DFG Research Fellow, 1994–1996, Virginia Commonwealth University (N. Farrell)
Research Associate, 1996–1998, Virginia Commonwealth University (N. Farrell)
Postdoctoral Research Associate, 1998–1999, University of Minnesota (L. Que, Jr.)
Description of Research
Research in our laboratory is concerned with the design of small-molecule agents for the cure and management of life-threatening diseases and for probing and modulating gene regulation. Structurally novel drugs and drug conjugates are prepared using organic and inorganic synthetic methodologies. The interactions of these agents with potential biomolecular targets (DNA, DNA-processing enzymes, metalloenzymes) are studied using bioanalytical (LC-MS) and high-resolution structural (NMR, X-ray) methods, as well as biophysical and molecular biology techniques. Biological activity studies are carried out in vitro and in vivo by collaborators at WFU School of Medicine. Our research is funded through the National Institutes of Health.
C. L. Smyre, G. Saluta, T. E. Kute, G. L. Kucera and U. Bierbach: Inhibition of DNA Synthesis by a DNA Platinating–Intercalating Hybrid Agent Leads to Potent Cell Kill in Non-Small Cell Lung Cancer. ACS Med. Chem. Lett; online ASAP.
H. Kostrhunova, J. Malina, A. J. Pickard, J. Stepankova, M. Vojtiskova, J. Kasparkova, T. Muchova, M. L. Rohlfing, U. Bierbach and V. Brabec: Replacement of a Thiourea with an Amidine Group in a Monofunctional Platinum–Acridine Antitumor Agent. Effect on DNA Interactions, DNA Adduct Recognition and Repair. Mol. Pharmaceutics; online ASAP.
L. A. Graham, G. M. Wilson, T. K. West, C. S. Day, G. L. Kucera and U. Bierbach: Unusual Reactivity of a Potent Platinum–Acridine Hybrid Antitumor Agent. ACS Med. Chem. Lett. 2:687 (2011).
J. Roy Choudhury, L. Rao and U. Bierbach: Rates of intercalator-driven platination of DNA determined by a restriction enzyme cleavage inhibition assay: J. Biol. Inorg. Chem. 16:373 (2011).
L. C. Eiter, N. W. Hall, C. S. Day, G. Saluta, G. L. Kucera and U. Bierbach: Gold(I) analogues of a platinum–acridine antitumor agent are only moderately cytotoxic but show potent activity against Mycobacterium tuberculosis. J. Med. Chem. 52:6519 (2009).
Z. Ma, J. Roy Choudhury, M. W. Wright, C. S. Day, G. Saluta, G. L. Kucera and U. Bierbach: A non-cross-linking platinum–acridine agent with potent activity in non-small-cell lung cancer. J. Med. Chem. 51:7574 (2008). L. Rao and U. Bierbach: Kinetically favored platination of adenine in the G-rich human telomeric repeat. J. Am. Chem. Soc. 129:15764 (2007).
Z. Ma, C. S. Day and U. Bierbach: Unexpected reactivity of the 9-aminoacridine chromophore in guanidylation reactions. J. Org. Chem. 72:5387 (2007).
C. G. Barry, C. S. Day and U. Bierbach: Duplex promoted platination of adenine-N3 in the minor groove of DNA: Challenging a longstanding bioinorganic paradigm. J. Am. Chem. Soc., 127:1160 (2005).
S. M. Hess, A. M. Mounce, R. C. Sequeira, T. M. Augustus, M. C. Ackley and U. Bierbach: Platinum-acridinylthiourea conjugates show cell line specific cytotoxic enhancement in H460 lung carcinoma cells compared to cisplatin. Cancer Chemother. Pharmacol. 56:337 (2005).
E. T. Martins, H. Baruah, J. Kramarczyk, G. Saluta, C. S. Day, G. L. Kucera and U. Bierbach: Design, synthesis and biological activity of a novel non-cisplatin-type platinum-acridine pharmacophore. J. Med. Chem., 44:4492 (2001).