ISOLATION OF BULK DEOXYNUCLEOSIDES FOR AIDS DRUGS

脱氧核苷目前正在发挥越来越大的作用 医药。几种实验性抗病毒艾滋病药物(AZT，DCC， 和DDA)是化学修饰的脱氧核苷。这些药物是 由于无法获得脱氧核苷，价格昂贵 合理的成本。脱氧核苷作为营养素也很受欢迎。 在用于生产单抗的哺乳动物组织培养中 以及其他具有重要医学价值的血液制品。稍加修改 真核DNA的组成成分是5-甲基脱氧胞嘧啶。这是必要的 用于研究基因表达调控和化学合成 重组DNA技术中使用的修改过的DNA片段。 考虑到对抗病毒药物和克隆血液产品的需求 以及时间和成本的重要性，以及第二阶段研究计划 建议立即提供特定的 脱氧核苷。拟议的研究包括四个具体的 片段：a)酶解反应的优化 同时降低脱氧核苷中的脱氨基水平 混合物，b)扩大离子萃取柱的规模并开发 最终纯化所需的二次色谱柱 每个脱氧核苷，c)最终确定程序以生产 晶体脱氧核苷和d)建立质量控制 提纯5-氨基丁酸的技术指标和方法探索 甲基脱氧胞嘧啶。成本分析表明，优化 第一阶段的创新将导致巨大的代价 还原脱氧核苷。

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.