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

“生命过程化学”项目将通过这一职业奖，支持密歇根大学的Mi Hee Lim教授设计和合成化学文库，以建立结构和与金属相关的β淀粉样蛋白相互作用之间的关系。在这个研究项目中，林教授和她的学生将确定与金属离子、β淀粉样蛋白和金属- β淀粉样蛋白相互作用所需的结构部分和支架。该研究小组将通过对小分子的系统结构修饰来合成多种化学系列，这些小分子先前被证明可以与淀粉样蛋白或金属淀粉样蛋白相互作用和反应。新制备的分子与金属离子、β -淀粉样蛋白和β -金属-淀粉样蛋白的相互作用将使用适当的分析方法，如紫外可见光谱和核磁共振光谱、质谱（MS）和x射线晶体学，进行全化学分辨率的表征。这项研究的结果将为开发化学工具提供见解，这些化学工具适用于研究金属-淀粉样蛋白在导致神经变性的神经毒性中的作用。由于目前尚不清楚金属离子与β -淀粉样蛋白的相互作用如何与神经毒性相关，因此有必要找到合适的化学工具，同时靶向金属- β -淀粉样蛋白并调节它们的相互作用。在这个研究项目中，Lim小组将为从高中到研究生水平的学生提供机会，进行生物无机化学的跨学科研究。传统上没有学习过这一领域的不同背景的学生不仅将学习生物无机化学的概念，而且还将在实验室中介绍令人兴奋的化学研究。林教授还将为女科学家（本科至博士后）创造专业发展机会，并特别关注与当地企业的接触、不同层次的女化学家之间的对话、持续的交流。通过这些努力，未来的女科学家将被鼓励加强她们对科学的参与，追求她们的职业目标。

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.