ENZYMATIC FORMATION OF POTENTIAL ANTICANCER AND ANTIVIRAL INOSINE ANALOGS

Theoretically, inosine analogues should act as effective inhibitors of tumor cell proliferation and viral replication To acquire a broad spe ctrum of new candidate inosine analogues, a rapid, facile, quantitativ e and stereoselective method for deaminating potential antitumor and a ntiviral adenine analogues previously synthesized in our laboratory wa s developed. A novel T-adenylic acid deaminase, with relaxed substrate requirements, from Aspergillus species was utilized to deaminate four hexofuranosyladenine nucleosides and five adenine nucleoside dialdehy des to their corresponding inosine analogues. The fastest rates of dea mination for the hexofuranosyl nucleosides were for the compounds wher e the vicinal hydroxyl groups on the sugars are oriented in the erythr o configuration. For rapid deamination of the adenine nucleoside diald ehydes, the R configuration at the proximal carbon atom is preferred, while the nature of the group on the distal carbon atom has no signifi cant effect on the rate or extent of deamination.