RUI: Developing Ion Mobility Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition & Redox Activity of Metal Ion Binding Oligopepti

在该项目中，由化学系化学结构、动力学机制B项目资助，德克萨斯农工大学-商学院化学系的Laurence Angel教授正在开发新型铜和锌螯合肽。铜和锌稳态的破坏直接涉及门克斯和威尔逊病以及癌症和神经系统疾病，如阿尔茨海默病和朊病毒病。金属螯合剂用于治疗这些类型的疾病。 该项目非常适合学生的跨学科培训，以支持不断增长的生物分析，蛋白质组学，生物工程和生物医学劳动力。 代表性不足的本科生群体，包括第一代大学生，非洲裔美国人，西班牙裔和女学生，将被鼓励加入研究工作。 更技术性地，替代金属结合肽（AMBS）和甲烷氧化菌素（mb-OB 3b）的溶液相金属离子反应性正在通过电喷雾离子迁移率质谱（IM-MS）和密度泛函理论（DFT）进行检查。紫外-可见和荧光光谱技术被用来检查气相和溶液相分析的相关性，以回答以下问题：（1）哪些溶液相行为可以在气相中检查？(2)pH依赖的金属离子结合是否会导致反映溶液相状态的带正电荷或负电荷的复合物？(3)哪些序列残基影响AMBS和mb-OB 3b金属离子结合？(4)AMBS和Zn（II）或Cu（I）阳离子化AMBS的碰撞诱导解离（CID）涉及哪些解离机制？(5)金属离子的配位位点能用能量分辨CID和IM-MS鉴定吗？(6)金属离子置换可以通过IM-MS滴定和碰撞截面变化来监测吗？(7)IM-MS分析和理论碰撞截面能否确定每种金属离子更喜欢哪种配位类型？(8)IM-MS、DFT、UV-Vis和荧光结果如何相互关联？ 该研究可以发现新的反应机制，开发更有效的IM-MS分子分析技术，同时朝着设计用于治疗与金属离子失衡相关疾病的螯合剂的方向发展。该奖项反映了NSF的法定使命，通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

In this project, funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Laurence Angel of the Department of Chemistry at Texas A&M University - Commerce is developing new classes of copper and zinc chelating peptides. Disruption of copper and zinc homeostasis is directly implicated in Menkes and Wilson's disease as well as cancers and neurological diseases, such as Alzheimer's and prion disease. Metal chelators are used in the treatment of these types of diseases. The project is well suited for the interdisciplinary training of students in support of the growing bioanalytical, proteomic, bioengineering, and biomedical workforce. Under-represented groups of undergraduate students, including first-generation college students, African-American, Hispanic, and female students, will be encouraged to join the research efforts. More technically, the solution-phase metal ion reactivity of alternative metal-binding peptides (AMBS) and methanobactin (mb-OB3b) is being examined by electrospray ionization ion mobility-mass spectrometry (IM-MS) and density functional theory (DFT). Ultraviolet-visible and fluorescence spectral techniques are being used to check for correlations across gas- and solution-phase analyses to answer the following questions: (1) Which solution-phase behaviors can be examined in the gas phase? (2) Does pH-dependent metal-ion binding result in positively or negatively charged complexes that reflect the solution-phase states? (3) Which sequence residues affect AMBS and mb-OB3b metal-ion binding? (4) Which dissociation mechanisms are involved in the collision-induced dissociation (CID) of AMBS and AMBS cationized by Zn(II) or Cu(I)? (5) Can the metal-ion coordination sites be identified using energy-resolved CID and IM-MS? (6) Can metal-ion displacement be monitored by IM-MS titrations and collision cross-section changes? (7) Can IM-MS analyses and theoretical collision cross-sections identify which type of coordination each metal ion prefers? (8) How do IM-MS, DFT, UV-Vis, and fluorescence findings correlate? The study could discover new reaction mechanisms and develop more effective IM-MS molecular analysis techniques, while moving toward the design of chelating agents for treating diseases related to metal-ion imbalance.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.