ISOLATION OF BULK DEOXYNUCLEOSIDES FOR AIDS DRUGS

用于艾滋病药物的大量脱氧核苷的分离

• 批准号: 3488793
• 负责人: JOSEPH A TOCE
• 金额: $ 5万
• 依托单位: RELIABLE BIOPHARMACEUTICAL CORPORATION
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1988-08-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3488793
• 关键词: DNA; alkaline phosphatase; antiAIDS agent; antiviral agents; biotechnology; chromatography; computers; deoxycytidine; deoxyribonuclease I; deoxyribonucleosides; health economics; high performance liquid chromatography; hydrolysis; ion exchange chromatography; phosphodiesterase I; thymidine; trout /salmon

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.

几种实验性抗病毒艾滋病药物（AZT，DDC，DDA） 基于化学修饰的脱氧核苷。 这些 脱氧核苷衍生物由核糖核苷制成， 不能以合理的成本获得脱氧核苷。 考虑到对抗病毒药物的需求以及 时间和成本，这是有意义的脱氧核苷可用 用于脱氧核苷衍生物的直接合成。 一个 详尽的文献检索表明苏联专利（1983， S#SU1，004，403）是唯一的参考，以指导我们的大 大规模生产这种有价值的材料。 一项研究计划被提出来填补这一空白，并协助 立即获得脱氧核苷。 拟议 研究由几个部分组成; a）大规模生产 来自鲑鱼的DNA，B）将DNA酶促水解成单- 核苷，然后去磷酸化为脱氧核苷 混合物，c）在不涉及盐的情况下分离脱氧核苷， 随后是材料的浓缩和d）质量控制 分离的脱氧核苷交叉污染。 在每个 在这种情况下，将使用新的方法来最大限度地减少生产 最终产品的时间和成本。 这项研究也是 预期产生5-甲基脱氧胞苷和6- 甲基脱氧腺苷，这是迫切需要研究 基因调控和表达机制。 的粗略估计 成本分析显示， 脱氧核苷与这个计划的成功。