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.

本研究的目的是阐明生物合成的起源， 从含氧硫氮杂卓（OTAP）的eudistomins的初级代谢产物 在海鞘Eudistoma olivacium中。 这些有效的抗病毒（HSV， Vaccina）代谢物似乎来源于色胺、半胱氨酸和 S-腺苷甲硫氨酸，尽管考虑了替代前体。 确定了生物合成途径沿着的潜在中间体， 提出了这些中间体的放射性标记合成。 使用 以前开发的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，这些假定的前体将进行测试， 掺入OTAP优泌肽。 双标记和降解 将采用方案来确定前体的特异性， 从而排除分解代谢过程，可能导致合并 放射性 OTAP生物合成研究的结果 eudistomins可能会导致后续的研究，旨在确定 E.编码这些代谢物的橄榄素 通过基因工程进行开发， 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。