In this project, we aim to develop a mass spectrometry (MS) method which has the capability of determining carbon-carbon double bond (C=C) locations in lipids and apply it to qualitative and quantitative lipidomic analysis. This project builds upon an innovation of coupling a photochemical reaction, the Patern-Bchi (PB) reaction, with electrospray ionization and tandem mass spectrometry (ESI-MS/MS). Through collision-induced dissociation (CID), the PB products of lipids fragment at the original C=C positions, allowing both C=C location determination and lipid quantitation for mixtures of lipid C=C position isomers. In this R01 project, research activities are proposed to develop and validate a fully integrated PB-MS/MS approach, with the following aims: (1) development and optimization of reaction and ionization conditions for on-line coupling of Patern-Bchi (PB) reaction with ESI-MS/MS, (2) development of MS/MS methods for structural determination and quantitation of unsaturated lipids of different classes, and (3) implementation and validation of PB-MS/MS method for lipidomic analysis. The Xia research group at Purdue University has the expertise in the development of analytical methods, MS instrumentation, and data analysis tools. The expected outcome from the project is to provide a robust and widely applicable MS platform with C=C specificity for lipidomics. A set of new knowledge will be generated for unsaturated lipids endogenous in rats/mice tissue samples including their C=C position information and composition of C=C position isomers. This new lipid analysis capabilities can potentially advance research in many fields in biological sciences, including but not limited to lipid molecular biology, functional lipidomics, metabolomics, and biomarker discovery.

Public Health Relevance

The proposed research can potentially lead to the development of a robust and widely applicable mass spectrometry (MS) platform for distinguishing and quantifying C=C lipid isomers from mixtures. It has strong relevance to general public health by providing a powerful tool to advance researches in lipid homeostasis, functional lipidomics, metabolomics, and disease diagnosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM118484-03
Application #
9518990
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Krepkiy, Dmitriy
Project Start
2016-07-01
Project End
2021-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Purdue University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Adhikari, Sarju; Yang, Xiaoyue; Xia, Yu (2018) Acetone/Isopropanol Photoinitiating System Enables Tunable Disulfide Reduction and Disulfide Mapping via Tandem Mass Spectrometry. Anal Chem 90:13036-13043
Ye, Zhishi; Adhikari, Sarju; Xia, Yu et al. (2018) Expedient syntheses of N-heterocycles via intermolecular amphoteric diamination of allenes. Nat Commun 9:721
Stinson, Craig A; Zhang, Wenpeng; Xia, Yu (2018) UV Lamp as a Facile Ozone Source for Structural Analysis of Unsaturated Lipids Via Electrospray Ionization-Mass Spectrometry. J Am Soc Mass Spectrom 29:481-489
Anglada, Josep M; Crehuet, Ramon; Adhikari, Sarju et al. (2018) Reactivity of hydropersulfides toward the hydroxyl radical unraveled: disulfide bond cleavage, hydrogen atom transfer, and proton-coupled electron transfer. Phys Chem Chem Phys 20:4793-4804
Adhikari, Sarju; Zhang, Wenpeng; Xie, Xiaobo et al. (2018) Shotgun Analysis of Diacylglycerols Enabled by Thiol-ene Click Chemistry. Anal Chem 90:5239-5246
Adhikari, Sarju; Xia, Yu (2017) Thiyl Radical-Based Charge Tagging Enables Sterol Quantitation via Mass Spectrometry. Anal Chem 89:12631-12635
Ren, Jia; Franklin, Elissia T; Xia, Yu (2017) Uncovering Structural Diversity of Unsaturated Fatty Acyls in Cholesteryl Esters via Photochemical Reaction and Tandem Mass Spectrometry. J Am Soc Mass Spectrom 28:1432-1441