Career: Total Synthesis and Study of the Molecular Recognition Determinants of Amanita Phalloides Toxins

职业：鹅膏菌毒素的全合成及分子识别决定因素研究

• 批准号: 9984227
• 负责人: Rodney Guy
• 金额: --
• 依托单位: University of California-San Francisco
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9984227&HistoricalAwards=false
• 关键词: Career; Total; Synthesis; Study; Molecular

The focus of this research is the development of synthetic methods for the preparation of amanitin and phalloidin. The synthetic strategy involves late introduction of problematic functionality and early introduction of the thioether bridges common to the two targets. The majority of the peptide backbone will be assembled using solid phase peptide synthesis. Analog studies will be used to allow understanding of the specific binding properties of amanitin to RNA polymerase II and phalloidin to polymerized actin. The educational focus of the project will be the development of a new graduate training program in Chemical Biology.With this CAREER award, the Organic and Macromolecular Chemistry Program is supporting the research and educational activities of Dr. Rodney K. Guy of the Department of Pharmaceutical Chemistry at the University of California-San Francisco. Dr. Guy will focus his research on the total synthesis and study of the molecular modes of action of two related natural products:amanitin and phalloidin. The natural products and synthetic analogs will be studied to understand the molecular determinants that drive the selectivity of binding for these compounds. The educational portion of the project involves curriculum development at the graduate level.

本研究的重点是鹅膏蕈碱和鬼笔环肽的合成方法的发展。 合成策略包括后期引入有问题的功能和早期引入两个目标共同的硫醚桥。 大部分肽骨架将使用固相肽合成来组装。 模拟研究将被用来允许的特定结合特性的鹅膏蕈碱RNA聚合酶II和鬼笔环肽聚合肌动蛋白的理解。 该项目的教育重点将是开发一个新的化学生物学研究生培训计划。有了这个CAREER奖，有机和高分子化学计划将支持Rodney K博士的研究和教育活动。加州大学圣弗朗西斯科弗朗西斯科药物化学系的盖伊说。 Guy博士将专注于两种相关天然产物的全合成和分子作用模式的研究：鹅膏蕈碱和鬼笔环肽。 将研究天然产物和合成类似物，以了解驱动这些化合物结合选择性的分子决定因素。 该项目的教育部分涉及研究生一级的课程编制。