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

在这个由化学学部化学结构、动态和机理B项目资助的项目中，德克萨斯农工大学商学院化学系的劳伦斯·安吉尔教授正在开发新型铜和锌螯合肽。铜和锌体内平衡的破坏与Menkes和Wilson病以及癌症和神经系统疾病（如阿尔茨海默氏症和朊病毒病）有直接关系。金属螯合剂用于治疗这类疾病。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工作人员。未被充分代表的本科生群体，包括第一代大学生、非裔美国人、西班牙裔和女学生，将被鼓励加入研究工作。从技术上讲，通过电喷雾离子迁移质谱（IM-MS）和密度泛函理论（DFT）研究了替代金属结合肽（AMBS）和甲烷obactin （mb-OB3b）的溶液相金属离子反应性。紫外-可见和荧光光谱技术被用于检查气相和溶液相分析之间的相关性，以回答以下问题：(1)哪些溶液相行为可以在气相中进行检查？(2) ph依赖的金属离子结合是否会产生反映溶液相状态的带正电或带负电的配合物？(3)哪些序列残基影响AMBS和mb-OB3b金属离子结合？(4) AMBS与Zn（II）或Cu(I)阳离子AMBS碰撞诱导解离（CID）涉及哪些解离机制？(5)能否利用能量分辨CID和IM-MS识别金属离子配位位点？(6)能否通过IM-MS滴定和碰撞截面变化监测金属离子位移？(7) IM-MS分析和理论碰撞截面能否确定每种金属离子偏好哪种类型的配位？(8) IM-MS， DFT， UV-Vis和荧光结果如何相关？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，同时为设计治疗金属离子失衡相关疾病的螯合剂奠定基础。该奖项反映了美国国家科学基金会的法定使命，并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.