• Design, synthesis, and study of enzyme inhibitors
• Anticancer and antiviral drug action and design
• Design and synthesis of nucleoside & nucleotide analogues

433 Hochstetter Hall Department of Chemistry University at Buffalo The State University of New York Buffalo, NY 14260-3000 Phone: (716) 645-6368 Fax: (716) 645-6963 E-mail: tkalman@buffalo.edu

• B.S./M.S. Technical University of Budapest
• Ph.D., University at Buffalo (1968)
• NIH Pre- and Postdoctoral Fellow (1967-70)
• Research Career Development Awardee, NIGMS, NIH (1971-76)
• Scholar of the American Cancer Society (1996-97)

Design, Synthesis and Study of Enzyme Inhibitors, Nucleoside & Nucleotide Analogues and Prodrugs; Design of Molecular Probes; Design of Organic Semiconductors; Study of Anticancer and Antiviral Drug Action and Resistance

Our laboratory has been engaged in a multidisciplinary anticancer and antiviral drug discovery research endeavor that utilizes a combination of mechanism-based and structure-based design strategies. Our drug discovery effort is focused on the design of mechanism-based inhibitors of key enzymes in nucleotide metabolism, which are responsible for the biosynthesis of the building blocks of DNA and RNA. These design strategies require a considerable insight into the molecular mechanisms of catalysis performed by the target enzymes, which are probed by kinetic and equilibrium isotope effect studies, and molecular modeling. Enzyme inhibitory activities of the compounds synthesized are determined using purified enzymes, as well as cellular enzyme systems. The following enzyme targets have been studied recently:

1. thymidylate synthase that is essential for de novo biosynthesis of DNA-thymine;
2. thymidine phosphorylase, also known as platelet derived endothelial cell growth factor, involved in tumor angiogenesis, a process required for the growth of solid tumors.

Selected Recent Publications