Boronic derivatization-based strategy for monoacylglycerol identification, isomer annotation and quantification

Area of Science:

• Biochemistry
• Analytical Chemistry
• Molecular Biology

Background:

• Monoacylglycerols (MAGs) are crucial signaling molecules implicated in various diseases.
• Challenges exist in the direct detection and isomer-specific annotation of MAGs, hindering comprehensive profiling and disease association studies.

Purpose of the Study:

• To develop a novel strategy for the unambiguous identification, isomer annotation, and quantification of MAGs in biological samples.
• To address the limitations in MAG standard availability and the instability of certain isomers.

Main Methods:

• A boronic derivatization strategy using 3-nitrophenylboronic acid was employed for MAG analysis.
• A prediction model integrating mass spectrometry data (m/z, isotopic distribution) and chromatographic retention time was established for MAG identification.
• Distinguished fragmentation patterns of derivatized MAG isomers were utilized for unambiguous annotation.

Main Results:

• The developed method successfully enabled the capture and detection of thermally unstable sn-2 MAG isomers.
• Novel fragmentation patterns provided unambiguous annotation of MAG isomers.
• The strategy was applied to breast cancer samples, identifying MAGs as potential diagnostic biomarkers and chemotherapy indicators.
• A specific MAG isomer was linked to disease onset, challenging the holistic view of MAGs in disease.

Conclusions:

• The boronic derivatization strategy offers a robust solution for the unambiguous identification, annotation, and quantification of MAGs and their isomers in biological fluids.
• This approach is valuable for advancing mechanistic studies of diseases associated with MAG dysregulation, such as breast cancer.
• The findings highlight the potential of specific MAG isomers as biomarkers for disease diagnosis and treatment monitoring.