PYRIMIDINE NUCLEOSIDE PHOSPHORYLASES IN CHEMOTHERAPY

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The objectives of this grant proposal are: 1. Chemical synthesis of analogs and derivatives of BAU (5-benzylacyclouridine) and BBAU (5-benzyloxybenzylacyclouridine), potent inhibitors of uridine phosphorylase and potentiators of the anti-tumor action of FUdR, designed to improve facility of clinical use, to produce new anti-tumor drugs and pro-drugs, and to explore further their biological properties. 2. Biological testing of these new agents as inhibitors of uridine phosphorylase and, where indicated, thymidine phosphorylase, as transport inhibitors, anti-tumor agents and potentiators both in vitro and in vivo, and as tools for obtaining new biochemical knowledge related to nucleic acid metabolism. These studies will be performed in collaboration with colleagues in the Roger Williams Cancer Center.