CAREER: Understanding the Structure-Interaction-Reactivity Relationship between Small Molecules and Metal-Amyloid Species

职业：了解小分子和金属淀粉样蛋白之间的结构-相互作用-反应性关系

• 批准号: 1253155
• 负责人: Mi Hee Lim
• 金额: $ 55万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1253155&HistoricalAwards=false
• 关键词: CAREER; Understanding; Structure; Interaction; Reactivity

With this CAREER Award the Chemistry of Life Processes program is supporting Professor Mi Hee Lim at the University of Michigan to design and synthesize chemical libraries to establish a relationship between structures and interactions with metal-associated amyloid-beta species. In this research program Professor Lim and her students will determine the structural moieties and scaffolds required for interactions with metal ions, amyloid-beta, and metal-amyloid-beta species. The research group will synthesize multiple chemical series via systematic structural modifications of small molecules previously demonstrated to interact and react with amyloid-beta or metal-amyloid-beta species. The interactions of newly prepared molecules with metal ions, amyloid-beta, and metal-amyloid-beta species will be characterized to full chemical resolution using appropriate analytic methods, such as UV-Visible and NMR spectroscopy, mass spectrometry (MS), and X-ray crystallography.The results of this research effort will provide insight into the development of chemical tools suitable for investigating the involvement of metal-amyloid-beta species in neurotoxicity leading to neurodegeneration. Since it is not well understood how the interactions of metal ions with amyloid-beta species could be associated with neurotoxicity, it is necessary to have appropriate chemical tools that can simultaneously target metal-amyloid-beta species and modulate their interactions. In pursuing this research program, the Lim group will provide opportunities for students from high school through graduate student level to conduct interdisciplinary research in bioinorganic chemistry. Students with diverse backgrounds who traditionally have not studied this field will not only be taught the concepts of bioinorganic chemistry, but also will be introduced to exciting chemistry research in the laboratory. Professor Lim will also create professional development opportunities for female scientists (undergraduate to postdoctoral), with special attention to outreach to local companies, dialogue among different levels of female chemists, and continuous communication. Through these efforts, future female scientists will be encouraged to enhance their involvement in the sciences and pursue their career goals.

有了这个职业奖，生命过程化学计划支持密歇根大学的Mi Hee Lim教授设计和合成化学库，以建立结构与金属相关淀粉样蛋白β物种相互作用之间的关系。 在这项研究计划中，Lim教授和她的学生将确定与金属离子，淀粉样蛋白-β和金属-淀粉样蛋白-β物种相互作用所需的结构部分和支架。 该研究小组将通过对先前被证明与淀粉样蛋白β或金属淀粉样蛋白β物种相互作用和反应的小分子进行系统的结构修饰来合成多个化学系列。 新制备的分子与金属离子、淀粉样蛋白-β和金属-淀粉样蛋白-β物质的相互作用将使用适当的分析方法表征为完全化学分辨率，例如UV-可见光和NMR光谱、质谱（MS），和X射线晶体学。这项研究工作的结果将提供深入了解化学工具的发展，适用于调查金属淀粉样蛋白的参与，神经毒性中的β物质导致神经变性。 由于目前还不清楚金属离子与淀粉样蛋白-β物质的相互作用如何与神经毒性相关，因此有必要拥有适当的化学工具，可以同时靶向金属-淀粉样蛋白-β物质并调节它们的相互作用。 在追求这一研究计划，林集团将提供机会，从高中到研究生水平的学生进行跨学科的研究，在生物无机化学。 具有不同背景的学生谁传统上没有研究这一领域不仅将被教导生物无机化学的概念，而且还将被引入到令人兴奋的化学研究在实验室。 林教授还将为女科学家（本科到博士后）创造专业发展机会，特别关注与当地公司的联系，不同层次的女化学家之间的对话，以及持续的沟通。 通过这些努力，将鼓励未来的女科学家更多地参与科学工作，追求自己的职业目标。