This is an application for a New Investigator Research Award (NIRA). The analogs of adenosine and inosine are to be synthesized in which their pyrimidine ring will be replace with a 1,3-diazepine ring to obtain the corresponding 3- (Beta-D-ribofuranosy)-6H-imidazo[4,5-d][1,3]-diazepine derivatives. The proposed synthesis consists of the successive construction of the appropriately substituted imidazone nucleosides, followed by fusion of the diazepine ring with suitable annelating reagents which, if unknown, will be synthesized. The adenosine analog will be converted into the corresponding mono- and diphosphate derivatives, and the latter will be utilized to prepare the corresponding polynucleotide using the enzyme polynucleotide phosphorylase. A 'swollen' double-helix will be constructed by base-pairing this polynucleotide with poly(C), followed by investigation of its properties. These analogs will be evaluated for their potential antiviral activity as well as for the substate-inhibitory properties for the enzymes of the purine biosynthetic pathway.
