The scope of this project is to design and synthesize mechanism-based inhibitors of enzymatic reactions that are critical for the growth of neoplastic cells or viral replication. The resulting compounds are intended to be used as therapeutic agents and research probes. The following topics are of current interest: 1) Dinucleotide analogues of NAD as inhibitors of IMP dehydrogenase, 2) Acid-stable inhibitors of cytidine deaminase intended for oral use, 3) Synthesis of diazepinone nucleosides as dCMP deaminase inhibitors, 4) Synthesis of phosphonate analogues of the 2',5'-oligoadenylate trimer as stable inducers of interferon production, 5) Synthesis of purine phosphonates as inhibitors of purine nucleoside phosphorylase (PNP), 6) Synthesis of carbocyclic nucleosides as potential anti-viral agents.
