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

在这个项目中，由化学部化学结构、动态和机理B计划资助，德克萨斯农工大学商务部化学系的Laurence Angel教授正在开发新类别的铜和锌螯合肽。铜和锌动态平衡的破坏直接与门克斯和威尔逊病以及癌症和神经疾病有关，如阿尔茨海默氏症和普里恩病。金属螯合剂被用于治疗这些类型的疾病。该项目非常适合对学生进行跨学科培训，以支持不断增长的生物分析、蛋白质组、生物工程和生物医学劳动力。包括第一代大学生、非裔美国人、西班牙裔和女性学生在内的未被充分代表的本科生群体将被鼓励加入研究努力。采用电喷雾离子迁移率-质谱仪(IM-MS)和密度泛函理论(DFT)对替代金属结合肽(AMBS)和甲烷结合蛋白(mb-OB3b)的溶液相金属离子反应性进行了研究。紫外可见和荧光光谱技术正被用来检查气相和溶液相分析之间的相关性，以回答以下问题：(1)气相中可以检测到哪些溶液相行为？(2)依赖于pH的金属离子结合导致反映溶液相态的带正电荷的络合物还是负电荷的络合物？(3)哪些序列残基影响AMBS和MB-OB3b金属离子结合？(4)哪些解离机制涉及到锌(II)或铜阳离子对AMBS和AMBS的碰撞诱导解离(CID)(1)？(5)能用能量分辨的CID和IM-MS识别金属离子配位吗？(6)能用IM-MS滴定和碰撞截面变化监测金属离子的位移吗？(7)IM-MS分析和理论碰撞截面能确定每个金属离子更喜欢哪种配位类型吗？(8)IM-MS如何，DFT、UV-VIS和荧光结果是否相关？这项研究可以发现新的反应机理，开发更有效的IM-MS分子分析技术，同时朝着治疗与金属离子失衡相关的疾病的螯合剂的设计迈进。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.