Ph.D.: Iowa State University, 1968 Member of the University of Colorado Cancer Center and the Graduate Faculty of the School of Pharmacy, University of Colorado Health Sciences Center

Bio-Organic & Bio-Inorganic Nucleic Acids Chemical Biology/Genetics

Professor Koch and his students and co-workers are investigating aspects of bioorganic chemistry, medicinal chemistry, photochemistry, and free radical chemistry.They are particularly interested in the chemistry of the anthracycline quinone antitumor drugs, Adriamycin (doxorubicin), Epirubicin (epidoxorubicin) and Daunomycin (daunorubicin), relevant to their modes of biological activity and drug development. The research group has studied nucleic acid photochemistry and its application to the elucidation of protein nucleic acid interactions. The synthesis and properties of amino-carboxy-stabilized carbon radicals such as 3,5,5-trimethyl-2-oxomorpholin-3-yl (TM-3) was an earlier area of interest

Barthel, B.L.; Rudnicki, D.L.; Kirby, T.P.; Colvin, S.M.; Burkhart, D.J.; Koch, T.H.; Synthesis and Biological Characterization of Protease-Activated Prodrugs of Doxazolidine, J. Med. Chem., 55, 6595-6607 (2012).

Gold, L.; Ayers, D.; Bertino, J.; Bock, C.; Bock, A.; Brody, E.N.; Carter, J.; Dalby, A.; Eaton, B.E.; Fitzwater, T.; Flather, D.; Forbes, A.; Foreman, T.; Fowler, C.; Gawande, B.; Goss, M.; Gunn, M.; Gupta, S.; Halladay, D.; Heil, J.; Heilig, J.; Hicke, B.; Husar, G.; Janjic, N.; Jarvis, T.; Jennings, S.; Katilius, E.; Keeney, T.R.; Kim, N.; Koch, T.H.; Kraemer, S.; Kroiss, L.; Le, N.; Levine, D.; Lindsey, W.; Lollo, B.; Mayfield, W.; Mehan, M.; Mehler, R.; Nelson, S.K.; Nelson, M.; Nieuwlandt, D.; Nikradi, M.; Ochsner, U.; Ostroff, R.M.; Otis, M.; Perker, T.; Pietrasiewicz, S.; Schneider, D.; Singer, B.; Stanton, M.; Sterkel, A.; Stewart, A.; Stratford, S.; Vaught, J.D.; Vrkljan, M.; Walker, J.J.; Watrobka, M.; Waugh, S.; Weiss, A.; Wilcox, S.; Wolfson, A.; Wolk, S.; Zhang, C.; Zichi, D. “Aptamer-based multiplexed proteomic technology for biomarker discovery”, PLoS ONE 5(12) 2010: e15004. doi:10.1371/journal.pone.0015004.

Barthel, B.L.; Zhang, Z.; Rudnicki, D.L.; Coldren, C.D.; Polinkovsky, M.; Sun, H.; Koch, G.G.; Chan, D.C.F.; Koch, T.H. "Preclinical Efficacy of a Carboxylesterase 2-Activated Prodrug of Doxazolidine", J. Med. Chem. 2009, 52, 7678-7688.

Koch, T.H.; Barthel, B.L.; Kalet, B.T.; Rudnicki, D.L.; Post, G.C.; Burkhart, D.J. "Anthracycline-formaldehyde Conjugates and Their Targeted Prodrugs", Topics in Current Chemistry, 2008, 283, 141-170.

Spencer, D.M.; Bilardi, R.A.; Koch, T.H.; Post, G.C.; Nafie, J.W.; Kimura, K.-I.; Cutts, S..; Phillips, D.R. "DNA Repair in Response to Anthracycline-DNA Adducts: A Role for both Homologous Recombination and Nucleotide Excision Repair", Mutation Res. 2008, 638, 110-121.

Barthel, B.L.; Torres, R.C.; Hyatt, J.L.; Edwards, C.C.; Hatfield, M.J.; Potter, P.M.; Koch, T.H. "Identification of Human Intestinal Carboxylesterase as the Primary Enzyme for Activation of a Doxazolidine Carbamate Prodrug", J. Med. Chem. 2008, 51, 298-304.

Kalet, B.T.; McBryde, M.B.; Espinosa, J.M.; Koch, T.H. "Doxazolidine Induction of Apoptosis by a Topoisomerase II Independent Mechanism", J. Med. Chem. 2007, 50, 4493-4500.

Burkhart, D.J.; Barthel, B.L.; Post, G.C.; Kalet, B.T.; Nafie, J.W.; Shoemaker, R.K.; Koch, T.H. "Design, Synthesis, and Preliminary Evaluation of Doxazolidine Carbamates as Prodrugs Activated by Carboxylesterases", J. Med. Chem. 2006, 49, 7002-7012.

Post, G.C.; Barthel, B.L.; Burkhart, D.J.; Hagadorn, J.R.; Koch, T.H. "Doxazolidine, a Proposed Active Metabolite of Doxorubicin That Cross-links DNA", J. Med. Chem. 2005, 48, 7648-7657.

Burkhart, D.J.; Kalet, B.T.; Coleman, M.P.; Post, G.C.; Koch, T.H. "Doxorubicin-formaldehyde Conjugate Targeting μvb3 Integrin", Mol. Cancer Therap. 2004, 3, 1593-1604.

Burke, P.J.; Kalet, B.T.; Koch, T.H. "Antiestrogen Binding Site (AEBS) and Estrogen Receptor (ER) Mediate Uptake and Distribution of 4-Hydroxytamoxifen-targeted Doxorubicin-formaldehyde Conjugate in Breast Cancer Cells" J. Med. Chem. 2004, 47, 6509-6518.

Cogan, P.S.; Koch, T.H. "Studies of Targeting and Intracellular Trafficking of an Anti-Androgen-Doxorubicin-Formaldehyde Conjugate in PC-3 Prostate Cancer Cells Bearing Androgen Receptor-GFP Chimera", J. Med. Chem. 2004, 47, 5690-5699.

Cogan, P.S.; Fowler, C.R.; Post, G.C.; Koch, T.H. "Doxsaliform: A novel N-Mannich base prodrug of a doxorubicin-formaldehyde conjugate", Lett. Drug Design Dis., 2004, 1, 247-255.

Burke, P.J.; Koch, T.H. "Design, Synthesis, and Biological Evaluation of Doxorubicin-Formaldehyde Conjugates Targeted to Breast Cancer Cells" J. Med. Chem. 2004, 47, 1193-1206.

Koch, T.H.; Smith, D.; Tabacman, E.; Zichi, D. A. "Kinetic Analysis of Site-specific Photoaptamer-Protein Cross-Linking" J. Mol. Biol. 2004, 336, 1159-1173.

Cogan, P.S.; Koch, T.H. "Rational Design and Synthesis of Androgen Receptor Targeted Non-Steroidal Anti-Androgen Ligands for the Tumor Specific Delivery of a Doxorubicin-Formaldehyde Conjugate", J. Med. Chem. 2003, 46, 5258-5270.

Smith, D.; Collins, B. D.; Heil, James, Koch, T. H. "Sensitivity and Specificity of Photoaptamer Probes" Mol. Cell. Proteomics, 2003, 2.1, 11-18.