BIOSYNTHESIS OF THE ANTITUMOR ALKALOIDS OF CATHARANTHUS

长春花抗肿瘤生物碱的生物合成

• 批准号: 3186968
• 负责人: ALASTAIR I SCOTT
• 金额: $ 11.66万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3186968
• 关键词: antineoplastics; cell free system; drug design /synthesis /production; indoles; nuclear magnetic resonance spectroscopy; vinblastine; vincristine

Biosynthetic mapping of indole alkaloid biosynthesis in Catharanthus roseus will be studied using cell-free incubations from modified tissue cultures and plant homogenates. The rearrangements and transformations from tryptophan and secologanin up to the complex dimeric oncolytic alkaloids vinblastine and vincristine will be examined. The mechanisms operating in vivo will be applied to the economical synthesis of a wide range of dimeric alkaloids, hitherto only available in small amounts for biological activity evaluation, using the combined strategies of partial synthesis and enzymatic transformation. Genetic manipulation of C. roseus cells will allow novel alkaloids to be isolated as well as the opportunity to increase the yield of VLB and VCR in transformed plants. High-field NMR studies of plant metabolism will be developed.

吲哚生物碱生物合成的生物合成作图 将采用无细胞培养法对长春花进行研究 来自改良的组织培养物和植物匀浆。 的 色氨酸的重排和转化， 裂叶皂苷直至复合二聚体溶瘤生物碱 将检查长春碱和长春新碱。 的机制 在体内操作将适用于经济的合成， 广泛的二聚生物碱，迄今为止只有在小 生物活性评价的量，使用组合的 部分合成和酶转化策略。 C.的遗传操作。玫瑰细胞将允许新的生物碱 以及增加产量的机会 转化植物中的VLB和VCR。 将开发植物代谢的高场核磁共振研究。