Synthesis, chemistry and biochemistry of a family of "fat" nucleosides and nucleotides possessing the following 5:7-fused heterocyclic base systems will be studied: I) imidazo(4,5,e)(1,3,4)triazepine; II) imidazo(4,5-e)(1,4)diazepine; and III) imidazo(4,5,d)(1,3)diazepine. The novel rearrangement discovered in the heterocyclic system of category I will be further explored for wide synthetic utility. The mono- and diphosphate derivatives of nucleosides of category II will be prepared. The diphosphates will be polymerized by using the enzyme polynucleotide phosphorylase and the resulting homopolymer templates will be evaluated for substrate/inhibitory activity against Moloney murine leukemia virus (M-MuLV) reverse transcriptase. These studies will be extended to "fat" nucleoside/nucleotide systems of categories I & III. The target and intermediate nucleosides and heterocycles will be screened for potential antitumor activity by the National Cancer Institute. The ongoing collaborative arrangements with Professor E. De Clercq of Katholieke University, Leuven, Belgium will enable testing of the above compounds for antiviral activity in a broad range of viral assay systems. Preliminary studies on the 5:8-fused heterocylic systems will be continued. As a secondary goal, double helical complexes will be prepared by pairing the above "fat" nucleotide homopolymers with appropriate pyrimidine counterparts, and investigated for stability, stacking interactions and conformational characteristics.