ISOLATION OF BULK DEOXYNUCLEOSIDES FOR AIDS DRUGS

脱氧核苷目前正在发挥越来越大的作用， 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 昂贵的原因是在 合理的费用。 脱氧核苷作为营养素也很受欢迎 在用于生产单克隆抗体的哺乳动物组织培养物中， 以及其他具有医学意义的血液制品。 一个小的修改 真核生物DNA的组成部分是5-甲基脱氧胞嘧啶。 需要它 用于基因表达控制和化学合成的研究 用于重组DNA技术的修饰DNA片段。 考虑到抗病毒药物和克隆血液制品的需求 以及时间和成本的重要性，以及第二阶段研究计划 建议立即提供具体的 脱氧核苷 研究内容包括四个具体的 部分：a）酶水解反应的优化 同时降低脱氧核苷中的脱氨基水平 B）按比例放大离子排斥柱并开发离子排斥柱， 最终纯化所需的二级色谱柱 每种脱氧核苷，c）完成产品程序 结晶脱氧核苷和d）建立质量控制 规范和探索纯化5- 甲基脱氧胞嘧啶 成本分析表明， 第一阶段的创新将带来巨大的代价， 脱氧核苷的还原。

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.