BIOSYNTHETIC STUDIES OF EUDISTOMINS C E K AND L

EUDISTOMINS C E K 和 L 的生物合成研究

• 批准号: 2066247
• 负责人: BILL J BAKER
• 金额: $ 10.01万
• 依托单位: FLORIDA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2066247
• 关键词: Tunicata; antiviral agents; azepines; biological products; cell free system; drug design /synthesis /production; drug metabolism; pyridoindole; radionuclide double label; radiotracer; tritium

The objective of this research is to elucidate the biosynthetic origin, from primary metabolites, of the oxathiazepine-bearing (OTAP) eudistomins in the ascidian Eudistoma olivacium. These potently antiviral (HSV, Vaccina) metabolites seemingly derive from tryptamine, cysteinal and S-adenosylmethionine, although alternative precursors are considered. Potential intermediates along the biosynthetic path are identified and radiolabelled syntheses of these intermediates are proposed. Using cell-frree methodology previously developed to study biosynthesis in other colonial marine invertebrates, these putative precursors will be tested for incorporation into the OTAP eudistomins. Double-label and degradative schemes will be employed to determine the specificity of the precursors and thus rule out catabolic processes that might lead to incorporation of radioactivity. The results of this biosynthetic study of the OTAP eudistomins could lead to subsequent studies aimed at identification of genetic material in E. olivacium that codes for these metabolites. Exploitation via genetic engineering could then make available commercial quantities of these potential drugs, obviating the problem of limited natural-source availability.

这项研究的目的是阐明生物合成的起源， 来自含氧硫氮平 (OTAP) eudistomins 的初级代谢物 存在于海鞘 Eudistoma olivacium 中。 这些有效的抗病毒药物（HSV、 疫苗）代谢物似乎源自色胺、半胱氨酸和 S-腺苷甲硫氨酸，尽管也考虑替代前体。 鉴定并鉴定生物合成路径上的潜在中间体 提出了这些中间体的放射性标记合成。 使用 以前开发用于研究其他生物合成的无细胞方法 殖民海洋无脊椎动物，这些假定的前体将被测试 纳入 OTAP eudistomins。 双标签和降解 将采用方案来确定前体和的特异性 因此排除了可能导致掺入的分解代谢过程 放射性。 OTAP 生物合成研究的结果 eudistomins 可能会导致后续研究旨在鉴定 E. olivacium 中编码这些代谢物的遗传物质。 通过基因工程进行开发可以实现商业化 这些潜在药物的数量，避免了有限的问题 自然资源的可用性。