Tjarks, Werner

Werner Tjarks, Dr. rer. nat., is Assistant Professor of Medicinal Chemistry in the College of Pharmacy. He joined the faculty in 2001.

Nucleoside antimetabolites such as gemcitabine, cytarabine, cladribine, fludarabine, clofarabine, acyclovir, ganciclovir, brivudine, zidovudine, stavudine, and emtricitabine are prodrugs that are widely used as anticancer agents or antiviral agents and their importance continues to increase. These antimetabolites utilize nucleoside salvage pathways for their transformation into active nucleoside triphosphates. Irrespective of the final intracellular targets of the triphosphates, which primarily are human or viral DNA and their respective polymerases or reverse transcriptases, the rate-limiting key activation step of the prodrugs is usually the initial conversion of the nucleoside to the corresponding monophosphate by phosphorylating enzymes, often deoxynucleoside kinases. Thymidine kinase (TK) is one of these deoxynucleoside kinases. Most eukaryotes and prokaryotes and many DNA viruses code for proteins with thymidine kinase activity. However, among all approved nucleoside antimetabolites only the HIV prodrugs zidovudine and stavudine are activated by human thymidine kinase 1 (hTK1). This is probably due to the fact that TKs have the most stringent substrate specificity among all nucleoside kinases and that crystal structures for drug design have only become available very recently. Dr. Tjarks’ research activities focus on the in silico design, synthesis, and biological evaluation of inhibitors and substrates of TKs from e.g.  Bacillus anthracis and Epstein-Barr virus as well as from hTK1 for antibiotic, antiviral, and anticancer therapies.

Selected Publications

• Wu, W.;  Yang, W.; Barth, R.F.;  Kawabata, S.; Swindall, M.; Bandyopadhyaya, A.K.;  Tjarks, W.;  Khorsandi, B.;  Blue, T.E.;  Ferketich, A.F.; Yang, M.; Christoforidis, G.A.;  Sferra, T.J.;  Binns, P.J.;  Riley, K.J.;  Ciesielski, M.J.;  Fenstermaker, R.A. Molecular targeting and treatment of an EGF receptor positive glioma using boronated cetuximab. Clin. Cancer Res. 13, 1260-1268, 2007.
  
• Pan, X.; Wu, G.; Yang, W.; Barth, R.F.; Tjarks, W.; Lee, R. J.; Synthesis of Cetuximab-Immunoliposomes via a Cholesterol-Based Membrane Anchor for Targeting of EGFR, Bioconjugate. Chem., 18, 101-108, 2007.
  
• Carnrot, C.; Vogel, S.R.;  Byun, Y.; Wang, L.; Tjarks, W.;  Eriksson, S.; Phipps, A.J.; Evaluation of Thymidine Kinase as a Potential Target for Development of Nucleoside Analogs against Bacillus anthracis; Biol. Chem., 387, 1575-1581, 2006.
  
• Byun, Y.;  Narayanasamy, S.; Johnsamuel, J.;  Bandyopadhyaya, A.K.; Tiwari, R.;  Al-Madhoun, A.S.; Barth, R.F.;  Eriksson, S.; Tjarks, W. 3-Carboranyl Thymidine Analogues (3CTAs) and other Boronated Nucleosides for Boron Neutron Capture Therapy; Anti-Cancer Agents in Medicinal Chemistry, 6, 127-144, 2006.
  
• Wu, G.;  Barth, R.F.; Yang, W.;  Lee, R.J.;  Tjarks, W.;  Backer, M.V.;  Joseph M. Backer, J.M.; Boron Containing Macromolecules and Nanovehicles as Delivery Agents for Neutron Capture Therapy; Anti-Cancer Agents in Medicinal Chemistry, 6, 167-184, 2006.
  
• Thirumamagal, B.T.S.; Johnsamuel, J.; Cosquer, G.Y.; Byun, Y.; Yan, J.;  Narayanasamy, S.; Tjarks, W.; Barth, R.F.; Al-Madhoun, A.S.; Eriksson, S.; Boronated Thymidine Analogues for Boron Neutron Capture Therapy, Nucleosides, Nucleotides & Nucleic Acids, 25, 861-866, 2006.
  
• Yang, W.;  Barth, R.F.;  Wu, G.; Kawabata, S.; Sferra,  T. J.; Bandyopadhyaya, A.K.; Tjarks, W.;  Ferketich, A.K.;  Binns, P.J.; Riley,  K.J.; Coderre, J.A.; Ciesielski, M.J.;  Robert A. Fenstermaker, R.A.;  and Carol J. Wikstrand, C.J.; Molecular Targeting and Treatment of EGFRvIII Positive Gliomas Using Boronated Monoclonal Antibody L8A4, Clin. Cancer Res., 12,  3792-3802, 2006.
  
• Byun, Y., Tjarks, W.; Investigation of Zwitterionic 7-Ammomium-7,9-nido-m-Carborane. Tetrahedron Lett., 47, 5649-5652, 2006.
  
• Narayanasamy, S.; Thirumamagal, B.T.S.; Johnsamuel, J.;  Carnrot, C.; Byun, Y.; Cosquer, G.Y.; Yan, J.;  Bandyopadhyaya, A.K.; Tiwari, R.V.; Eriksson. S.; Tjarks, W. Hydrophilically-Enhanced 3-Carboranyl  Thymidine Analogues (3CTAs) for Boron Neutron Capture Therapy (BNCT) of Cancer, Bioorg. Med. Chem., 14, 6886 -6899, 2006.
  
• Bandyopadhyaya, A.K.; Tiwari, R.V.; Tjarks, W.; Comparative Molecular Field Analysis and Comparative Molecular Similarity Indices Analysis of Boron Containing Human Thymidine Kinase 1 Substrates, Bioorg. Med. Chem., 14, 6924-6932, 2006.
  
• Byun, Y;  Thirumamagal, B.T.S.; Yang, W.; Eriksson, S.; Barth, R.F.; Tjarks, W. ; Preparation and Biological Evaluation of 10B-Enriched N5-2OH:  A Promising Boron Delivery Agent for Boron Neutron Capture Therapy (BNCT) of  Brain Tumors; J. Med. Chem., 49, 5513-5523, 2006.
  
• Thirumamagal, B.T.S., Zhao, X. B.; Bandyopadhyaya, A.K.; Johnsamuel, J.; Tiwari, R.V.; Golightly, D.W., Patel, V.; Jehning, B.T.; Backer, M.V.; Backer, J.M.; Lee, R.J.; Barth, R.F.; Tjarks, W.; Liposomal Formulations of Boron-Containing Cholesterol Mimics for Boron Neutron CaptureTherapy (BNCT); Bioconjugate. Chem., 1141-1150, 2006.

Contact
e-mail: tjarks.1@osu.edu
phone:    +1 614 292-7624

The Ohio State University
College of Pharmacy
421 Parks Hall
500 West 12th Avenue
Columbus, OH 43210-1291, USA

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