The objective of this project is to design and synthesize mechanism-based inhibitors of enzymatic reactions that are critical for the growth of neoplastic cells. The resulting compounds are intended to be used as therapeutic agents and research probes. The following topics are of current interest: 1) Synthesis of cyclopentenyl nucleosides (Neplanocin A analogs), 2) Dinucleotide analogs of NAD as IMPD inhibitors, 3) Transition-state inhibitors of cytidine triphosphate (CTP synthetase, 4) Synthesis of diazepinone nucleosides as fradulent uridine and cytidine analogs and 5) Synthesis of stable analogs of 2',5'-oligo-adenylate trimer as inducers of interferon production.
