Copper(II) For Isomer Elucidation from Lipid Dissociations by tandem Mass Spectrometry – CopperField-MS

Lipids are a heterogeneous class of biomolecules involved in energy storage, signaling, and modulation of membrane protein functions. Lipids are complex metabolites with significant structural and functional diversity, due in particular to the coexistence of multiple isomers. Lipids' molecular structure and biological functions are closely linked, making crucial accurate annotations of these compounds. Structural characterization at the isomeric level of complex lipids such as glycerophospholipids (GPLs) therefore offers an opportunity to improve understanding of the relationship between lipid metabolism and their biological activities. Since it has been demonstrated that GPLs carrying a particular double bond position could be biomarkers of various diseases, the development of an analytical method at the isomeric level would represent a significant advance for the early diagnosis of many diseases.
The CopperField-MS project aims to develop an easy-to-use, sensitive, and robust MS method based on copper adduction to characterize complex lipids at all isomeric levels. Beyond the fundamental insights into gas-phase reactivity and conformation of copper-adducted lipids that this project is designed to provide, it will also help to overcome current analytical barriers to the isomer-scale annotation of complex lipids. Copper-mediated tandem mass spectrometry (MS/MS) will be used to succeed in this project using different hyphenated separative methods such as chromatography and ion mobility spectrometry (IMS).
The objectives of this project are multiple and will enable us to understand and formalize the results obtained by MS/MS from copper complexes using spectroscopic and spectrometric methods. Using chromatographic and IMS couplings will extend the possibilities offered for the structural characterization of complex lipids to the analysis of complex samples. In addition, we will simplify the annotation of MS/MS spectra through the development of software that can be implemented in the classic lipidomics workflow. The results of this project will have multiple implications for lipidomics, as there is currently no method for fully resolving the isomeric structure of complex lipids using a single instrument.