中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Quaternized Acridine Maleimide MALDI Probe Enables Mass Spectrometry Imaging of Thiols

文献类型：期刊论文

作者Ma, Zhenghua6,7,8,9; Yuan, Jie5; Xu, Jianfeng3,4; Li, Lizhi6,7,8,9; Tang, Chunping9; Chang, Lu5; Quinn, Ronald J.2; Qin, Lunxiu3,4; Liu, Jia1,5; Ye, Yang6,7,8,9
刊名ANALYTICAL CHEMISTRY
出版日期2022-10-21
页码8
ISSN号0003-2700
DOI10.1021/acs.analchem.2c02292
通讯作者Qin, Lunxiu(qinlx@fudan.edu.cn) ; Liu, Jia(jia.liu@simm.ac.cn) ; Ye, Yang(yye@simm.ac.cn)
英文摘要Thiols are essential metabolites associated with redox imbalances and metabolic disorders in diseases. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) facilitates imaging of metabolites in tissue, but imaging of thiols remains challenging. Here we developed a method to visualize thiols using a stable isotope-labeled (SIL) MALDI probe, a mixture of unlabeled and deuterium-labeled reagents that provided adduct signals at [M]+ and [M + 3]+, to identify endogenous thiols in tissue. A series of MALDI probe candidates were rationally designed, and the structure-effect relationships were determined. First, the reactivity of different warheads toward the thiol group was evaluated, and maleimide was the best for in situ derivatization. Second, an acridine fragment showed the best improvement in MS responses. Third, a permanent charge was introduced for detection improvement in the positive mode. Finally, the hydrogens of methyl group were replaced by deuterium atoms, obtaining the novel SIL MALDI probe and thus facilitating significantly the annotation of thiols. The finally obtained D0/D3-9-((2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)carbamoyl)-10-methylacridin-10-ium iodide (D0/D3-MaI-MADA) enabled direct MSI of thiols in the fine structures of human liver tumors without a reduction procedure. Our work built a SIL MALDI probe for the first time and provided a strategy for the rational design of MALDI probes.
WOS关键词DISTRIBUTIONS ; GLUTATHIONE
资助项目National Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality ; Key Area Research and Development Program of Guangdong Province ; Shanghai Municipal Science and Technology Major Project ; [21920102003] ; [20430780300] ; [2020B0303070002]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000877148200001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/303002]  
专题新药研究国家重点实验室
通讯作者Qin, Lunxiu; Liu, Jia; Ye, Yang
作者单位1.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310058, Peoples R China
2.Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld 4111, Australia
3.Fudan Univ, Canc Metastasis Inst, Shanghai 201206, Peoples R China
4.Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai 200040, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, Nat Prod Chem Dept, Shanghai 201203, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Zhenghua,Yuan, Jie,Xu, Jianfeng,et al. Quaternized Acridine Maleimide MALDI Probe Enables Mass Spectrometry Imaging of Thiols[J]. ANALYTICAL CHEMISTRY,2022:8.
APA Ma, Zhenghua.,Yuan, Jie.,Xu, Jianfeng.,Li, Lizhi.,Tang, Chunping.,...&Ye, Yang.(2022).Quaternized Acridine Maleimide MALDI Probe Enables Mass Spectrometry Imaging of Thiols.ANALYTICAL CHEMISTRY,8.
MLA Ma, Zhenghua,et al."Quaternized Acridine Maleimide MALDI Probe Enables Mass Spectrometry Imaging of Thiols".ANALYTICAL CHEMISTRY (2022):8.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。