- Anticancer and antiviral nucleosides
- Boron chemistry
- Drug delivery
Nucleosides for anticancer and antiviral therapies
Nucleoside antimetabolites such as gemcitabine, fludarabine, clofarabine, acyclovir, ganciclovir, and zidovudine are bioprecursor prodrugs that are widely used as anticancer- 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 very stringent substrate specificities. Dr. Tjarks’ research activities focus on the in silico design, synthesis, and biological evaluation of inhibitors and substrates of hTK1 and TKs from viruses, such as the Epstein-Barr virus, for anticancer and antiviral therapies.
A second research focus of Dr. Tjarks’ group is the synthesis of boron cluster radiohalogenated therapeutics and imaging agents. Most radiopharmaceutical biomolecules (e.g. antibodies, carbohydrates, growth factors) that contain radiohalogenated boron clusters are less susceptible to dehalogenation under physiological conditions than their counterparts containing conventional radiohalogen-carbon bonds. There is an unexplored potential for such boron cluster radiohalogenated biomolecules to be used in the radiotherapy and imaging of cancer.
A third research focus of Dr. Tjarks' group is the design and synthesis of nanoparticle prodrugs of anticancer agents, such as Bortezomib, to increase tumor selectivity and reduce unwanted side effects.
- Recipient of the 2009 Miriam R. Balshone Memorial Award For Distinguished Teaching in the PharmD Program of The Ohio State University
- Dr. rer. nat., 1989, University of Bremen, Germany
- MS, 1986, University of Bremen
- Eur J Med Chem. 2015 Jul 15;100:197-209
- Bioorg Med Chem. 2015 Feb 1;23(3):532-47
- Nucleosides Nucleotides Nucleic Acids. 2014;33(12):786-99
- J Pharmacol Exp Ther. 2013 Nov;347(2):388-97
- Future Med Chem. 2013 Apr;5(6):677-92
- Eur J Med Chem. 2013 Feb;60:456-68
- Inorg Chem. 2012 Jan 2;51(1):629-39
- Tetrahedron Lett. 2011 Oct 26;52(43):5664-5667
- J Neurooncol. 2009 Dec;95(3):355-65
- J Chem Inf Model. 2009 Jun;49(6):1581-9