CAREER: Lipid Mass Tags Designed Via Selective Dissociation

职业：通过选择性解离设计的脂质质量标签

• 批准号: 2145487
• 负责人: Xin Yan
• 金额: $ 62.5万
• 依托单位: Texas A&M University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2145487&HistoricalAwards=false
• 关键词: CAREER; Lipid; Mass; Tags; Designed

With support from the Chemical Measurement and Imaging program in the Division of Chemistry, Xin Yan and her group at Texas A&M University are working to develop novel approaches to characterizing unsaturated lipids (fatty acids/esters) using mass spectrometry. Changes in the concentrations of lipid species in biological systems occur after perturbation by physiological processes, hence knowing the structures and concentrations of lipids is essential to elucidate their roles in physiological and pathological processes. Dr. Yan and her group are developing approaches to allow accurate quantification of multiple unsaturated lipids (including difficult-to-detect non-polar lipids) in a single experiment. The integrated educational plan seeks to amplify the scientific impact by broadening access to chemical education and chemical measurement research including live demos of fun experiments, engagement of students in chemistry open houses, and providing research opportunities for undergraduates.Accurate quantification of a lipid mixture with isomeric resolution has been a long-standing challenge. To address this challenge, a set of isobaric lipid mass tags (LMTs) is being designed to react selectively with lipid double bonds. By designing and tuning the LMT chemistry, diagnostic ions for determining double bond isomers are selectively produced in low energy collision-induced dissociation. Charged mass reporters corresponding to lipids from different samples are released upon higher energy dissociation, thereby enabling accurate quantitation of lipids from multiplexed samples in a single run. The combination of information from the two tandem MS experiments in a single run enables the quantification and identification of unsaturated lipid isomers. Development of LMTs will facilitate future investigations into lipid structure/function relationships. Broader impacts of the educational plan include promoting interest in and broadening access to chemical education and chemical measurement research for all levels of students. Disseminating science through live demos seeks to motivate middle/high school students to appreciate science at an early stage. Providing active engagement in experiments is seen as a good, hands-on approach to encouraging students to consider pursuing careers in STEM (Science, Technology, Engineering and Mathematics)-related fields. The innovation X program and research training are expected to provide undergraduate and graduate students with opportunities to work with advanced analytical technologies and develop new strategies for unsolved chemical measurement problems.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.

在化学系化学测量和成像项目的支持下，Xin Yan和她在德克萨斯A M大学的团队正在努力开发使用质谱法表征不饱和脂质（脂肪酸/酯）的新方法。生物系统中脂质物质浓度的变化发生在生理过程的扰动之后，因此了解脂质的结构和浓度对于阐明它们在生理和病理过程中的作用至关重要。Yan博士和她的团队正在开发一种方法，可以在一个实验中准确定量多种不饱和脂质（包括难以检测的非极性脂质）。该综合教育计划旨在通过扩大化学教育和化学测量研究的机会来扩大科学影响，包括有趣实验的现场演示，学生参与化学开放日，并为本科生提供研究机会。通过异构体分辨率准确定量脂质混合物一直是一个长期的挑战。为了应对这一挑战，一组同量异序脂质质量标签（LMT）被设计为选择性地与脂质双键反应。通过设计和调整LMT化学，用于确定双键异构体的诊断离子在低能量碰撞诱导解离中选择性地产生。对应于来自不同样品的脂质的带电质量报告物在较高能量解离时释放，从而能够在单次运行中准确定量来自多重样品的脂质。在单次运行中将来自两个串联MS实验的信息组合使得能够定量和鉴定不饱和脂质异构体。LMT的发展将促进未来的调查脂质结构/功能的关系。教育计划的更广泛影响包括促进各级学生对化学教育和化学测量研究的兴趣并扩大其获得机会。通过现场演示传播科学旨在激励初中/高中学生在早期阶段欣赏科学。提供积极参与实验被认为是一个很好的，动手的方法，鼓励学生考虑追求职业生涯在干（科学，技术，工程和数学）相关领域。创新X计划和研究培训有望为本科生和研究生提供使用先进分析技术的机会，并为未解决的化学测量问题开发新的策略。该奖项反映了NSF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。

项目成果

Lipid Mass Tags via Aziridination for Probing Unsaturated Lipid Isomers and Accurate Relative Quantification**

通过氮丙啶化的脂质质量标签用于探测不饱和脂质异构体和准确的相对定量**

• DOI: 10.1002/anie.202207098
• 发表时间: 2022
• 期刊: Angewandte Chemie International Edition
• 作者: Yang, Tingyuan;Tang, Shuli;Kuo, Syuan‐Ting;Freitas, Dallas;Edwards, Madison;Wang, Hongying;Sun, Yuxiang;Yan, Xin
• 通讯作者: Yan, Xin