BIOSYNTHESIS OF THE ANTITUMOR ALKALOIDS OF CATHARANTHUS

长春花抗肿瘤生物碱的生物合成

• 批准号: 3186970
• 负责人: ALASTAIR I SCOTT
• 金额: $ 12.18万
• 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/3186970
• 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.

吲哚生物合成的生物合成图 Catharanthus Roseus将使用无细胞孵化来研究 来自改良的组织培养物和植物匀浆。 这 色氨酸的重排和转换 secologanin直至复杂的二聚体肿瘤生物碱 Vinblastine和Vincristine将进行检查。 机制 体内操作将应用于经济合成 多种二聚体生物碱，迄今仅可用 使用合并的生物活动评估量 部分合成和酶促转化的策略。 玫瑰梭菌细胞的遗传操纵将允许新型生物碱 隔离以及有机会提高产量 VLB和VCR在转化的植物中。 将开发对植物代谢的高场NMR研究。