TAXOL AND TAXANES FROM PLANT TISSUE CULTURE

来自植物组织培养的紫杉醇和紫杉烷

• 批准号: 3199559
• 负责人: CHING-JER CHANG
• 金额: $ 24.9万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-20 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3199559
• 关键词: Agrobacterium; Conifera; antineoplastics; athymic mouse; biotechnology; chemical synthesis; clone cells; cytotoxicity; drug design /synthesis /production; drug screening /evaluation; gene expression; genetic promoter element; genetically modified plants; growth media; high performance liquid chromatography; immunologic assay /test; mass spectrometry; medicinal plants; nonhuman therapy evaluation; nuclear magnetic resonance spectroscopy; paclitaxel; plant extracts; tissue /cell culture; transfection

This project is aimed at developing plant tissue biotechnology for the production of taxol and taxol efflux blockers to improve the availability of taxol for further clinical evaluations and overcome taxol-resistance problems. This objective will be accomplished by a consortium which is multidisciplinary (analytical chemistry, biochemistry, natural product chemistry, molecular biology, and pharmacology) and multi-institutional (Purdue University and Upjohn Company). We propose to: (1) develop suspension tissue cultures and hairy root cultures of Taxus species; (2) analyze and select high yielding colonies by tubulin stabilization and tandem mass spectrometry/high performance liquid chromatography; (3) develop highly sensitive and compound-selective tandem mass spectrometric methods for taxol and other taxanes; (4) enhance production of taxol and desirable taxanes by induction with elicitors and transformation with various Agrobacterium strains; (5) prescreen potential taxol efflux blockers from tissue cultures; (6) perform biological and physical assay- directed isolation, and elucidate the structures of desirable constituents; (7) synthesize taxol from baccatin III or other related taxanes; and (8) evaluate antitumor activity of novel taxanes in vivo.

该项目旨在开发植物组织生物技术 生产紫杉醇和紫杉醇外排阻滞剂以提高可用性 紫杉醇用于进一步的临床评估并克服紫杉醇耐药性 问题。 这一目标将由一个财团来实现，该财团是 多学科（分析化学、生物化学、天然产物 化学、分子生物学和药理学）和多机构 （普渡大学和 Upjohn 公司）。 我们建议：（1）发展 红豆杉属植物的悬浮组织培养物和毛状根培养物； (2) 通过微管蛋白稳定分析和选择高产菌落 串联质谱/高效液相色谱； (3) 开发高灵敏度和化合物选择性串联质谱 紫杉醇和其他紫杉烷的测定方法； (4)提高紫杉醇产量 通过诱导子诱导和转化获得所需的紫杉烷 各种农杆菌菌株； (5) 预筛选潜在的紫杉醇外排 来自组织培养物的阻断剂； (6) 进行生物和物理测定- 定向分离，并阐明所需成分的结构； (7)以浆果赤霉素III或其他相关紫杉烷为原料合成紫杉醇；和（8） 评估新型紫杉烷的体内抗肿瘤活性。