ISOLATION OF BULK DEOXYNUCLEOSIDES FOR AIDS DRUGS

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Several experimental anti-viral AIDS drugs (AZT, DDC, DDA) are based on chemically modified deoxynucleosides. These deoxynucleoside derivatives are made from ribonucleosides due to the unavailability of the deoxynucleosides at a reasonable cost. Considering the need for anti-viral drugs and the importance of time and cost, it makes sense to have deoxynucleosides available for direct synthesis of deoxynucleoside derivatives. An exhaustive literature search indicates that a USSR patent (1983, S#SU1,004,403) is the only reference to guide us on the large scale production of this valuable material. A research program is proposed to fulfill this void and to assist in the immediate availability of deoxynucleosides. The proposed research consists of several segments; a) large-scale production of DNA from salmon, b) enzymatic hydrolysis of DNA to mono- nucleosides followed by dephosphorylation to a deoxynucleoside mixture, c) separation of deoxynucleosides without involving salts, followed by concentration of the material and d) quality control for cross-contamination of isolated deoxynucleosides. In each case, novel approaches will be used to minimize the production time and cost of the final products. This research is also expected to produce 5-methyldeoxycytidine and 6- methyldeoxyadenosine which are urgently needed to study the mechanism of gene control and expression. A rough estimate of cost-analysis indicates up to 90 percent price reduction of deoxynucleosides with the success of this program.