ISOLATION OF BULK DEOXYNUCLEOSIDES FOR AIDS DRUGS

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) ISTHE 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 MONONUCLEOSIDES 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.