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Article Abstract
The detection of glycosylation alterations is essential for elucidating the roles of glycan functions in biological processes and identifying potential disease biomarkers. Stable isotopic chemical labeling, coupled with mass spectrometry (MS), represents a powerful approach in quantitative glycomics. In this study, we synthesized a novel isotopic hydrazide pair, 2,6-Dimethyl-4-chinolincarbohydrazid (DMQCH) and its deuterium isomer DMQCH-d, via an efficient and cost-effective method, and applied it for the first time in MALDI-MS-based quantitative glycomics. The hydrazide tags, DMQCH/DMQCH-d, enabled stable mass shifts through reductive-terminal reactions with glycans, allowing for differential mass tagging of two samples without additional purification after derivatization. This DMQCH/DMQCH-d pair exhibited high derivatization efficiency (including on-target derivatization), substantial improvements in MS signal intensity (a 15-fold increase for maltoheptaose, high reproducibility (CV < 13.6 %), and excellent linearity (R > 0.99) over two orders of magnitude in dynamic range for the relative quantitative analysis of maltoheptaose. Furthermore, this isotopic hydrazide pair was validated by successfully measuring changes in serum N-glycan profiles from individuals with healthy human serum control and ovarian cancer, highlighting its potential in quantitative glycomics for clinical applications.
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| http://dx.doi.org/10.1016/j.talanta.2025.127921 | DOI Listing |
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