ISOLATION OF BULK DEOXYNUCLEOSIDES FOR AIDS DRUGS

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Deoxynucleosides are currently playing an increasing role in medicine. Several experimental anti-viral AIDS drugs (AZT, DCC, AND DDA) are chemically modified deoxynucleosides. These drugs are expensive due to the unavailability of deoxynucleosides at reasonable costs. Deoxynucleosides are also in demand as nutrients in mammalian tissue cultures used to produce monoclonal antibodies and other medically significant blood products. A minor modified component of eukaryotic DNA is 5-methyldeoxycytosine. It is needed for the study of gene expression control and for chemical synthesis of modified DNA fragments used in recombinant DNA technology. Considering the need for anti-viral drugs and cloned blood products and the importance of time and cost, and Phase II research program is proposed for the immediate availability of specific deoxynucleosides. The proposed research consists of four specific segments: a) optimization of the enzymatic hydrolysis reaction while reducing the level of deamination in the deoxynucleoside mixture, b) scaling up the ion-exlusion column and developing the secondary chromatographic column required for final purification of each deoxynucleoside, c) finalize procedures to product crystalline deoxynucleosides and d) establish quality control specifications and explore methods for purifying 5- methyldeoxycytosine. Cost analysis indicates that optimization of the Phase I innovations will result in a significant price reduction of deoxynucleosides.