CAREER: Chemical and Biological Studies on Natural Modulators of Cell Signaling

职业：细胞信号天然调节剂的化学和生物学研究

• 批准号: 0513160
• 负责人: Dennis Wright
• 金额: $ 24.07万
• 依托单位: Dartmouth College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-09 至 2006-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0513160&HistoricalAwards=false
• 关键词: CAREER; Chemical; Biological; Studies; Natural

The proposed research focusses on the total synthesis of two classes of natural products, the cyathins and the viridins. Construction of key intermediates via an electrochemical ring closure will be investigated in both cases. The cyathins have been shown to upregulate the synthesis of nerve growth factor while the viridins are inhibitors of phosphatidylinositol 3-kinase, a key signaling enzyme linked to cell growth and cancer. The design and synthesis of analogs of both classes of natural product will be carried out and their biological activity will be evaluated by collaborators of Professor Wright. Professor Wright will organize his undergraduate organic chemistry class into "learning communities" of 5-8 students. These groups will meet for one hour per week outside of lecture for problem-solving workshops. A further innovation will be to have the student groups design a short (3-5 step) synthesis of a potential drug candidate that would then be carried out for Professor Wright's research group. With this CAREER award, the Organic Synthesis program is supporting the research of Professor Dennis Wright of the Department of Chemistry at the University of Florida. Professor Wright's studies are directed towards the synthesis of two classes of natural products, the cyathins and the viridins. The cyathins (and possibly their analogs) stimulate nerve growth factor (NGF) synthesis and could potentially be used in place of exogenous NGF administration. The viridins (and possibly their analogs) inhibit an enzyme associated with cell growth and could potentially be used as antitumor agents. The education component of the project will introduce problem-solving and synthesis design sessions into the undergraduate organic chemistry course.

建议的研究集中在两类天然产物的全合成，cyathins和viridins。 通过电化学闭环的关键中间体的建设将在这两种情况下进行调查。 已经证明，胞苷肽上调神经生长因子的合成，而绿蛋白是磷脂酰肌醇3-激酶的抑制剂，磷脂酰肌醇3-激酶是与细胞生长和癌症相关的关键信号酶。 这两类天然产物的类似物的设计和合成将由Wright教授的合作者进行，并评估其生物活性。 赖特教授将他的本科有机化学班组织成5-8名学生的“学习社区”。 这些小组将每周在讲座之外举行一小时的解决问题研讨会。 进一步的创新将是让学生小组设计一个简短的（3-5步）合成一种潜在的候选药物，然后为赖特教授的研究小组进行。有了这个职业奖，有机合成计划是支持化学系教授丹尼斯赖特在佛罗里达大学的研究。 Wright教授的研究方向是合成两类天然产物，即cyathins和viridins。 该cathins（和可能的它们的类似物）刺激神经生长因子（NGF）的合成，并可能被用于替代外源性NGF管理。 病毒素（可能还有它们的类似物）抑制一种与细胞生长相关的酶，并可能用作抗肿瘤剂。 该项目的教育部分将把解决问题和合成设计课程引入本科有机化学课程。