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Isotope-coded hydrazide tags for MALDI-MS based quantitative glycomics.

Jian Fei1, Si Liu2, Qiuyue Sha1

  • 1The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics, Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

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PubMed
Summary
This summary is machine-generated.

A new chemical labeling method using DMQCH/DMQCH-d4 hydrazides enables precise quantitative glycomics. This technique improves mass spectrometry signal and is effective for detecting disease biomarkers in clinical samples.

Keywords:
2,6-Dimethyl-4-chinolincarbohydrazidIsotope-code hydrazideMALDI-MSQuantitative glycomics

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Area of Science:

  • Biochemistry
  • Analytical Chemistry
  • Biomarker Discovery

Background:

  • Glycosylation alterations are crucial for understanding biological processes and identifying disease biomarkers.
  • Quantitative glycomics, particularly using stable isotopic chemical labeling and mass spectrometry (MS), is vital for this analysis.

Purpose of the Study:

  • To develop and apply a novel isotopic hydrazide pair for efficient and cost-effective quantitative glycomics.
  • To validate the utility of this new labeling method in analyzing glycan profiles for potential clinical applications.

Main Methods:

  • Synthesis of a novel isotopic hydrazide pair: 2,6-Dimethyl-4-chinolincarbohydrazid (DMQCH) and its deuterium isomer DMQCH-d4.
  • Application of DMQCH/DMQCH-d4 for stable mass tagging of glycans via reductive-terminal reactions in MALDI-MS-based quantitative glycomics.
  • Validation using maltoheptaose for derivatization efficiency, MS signal enhancement, reproducibility, and linearity.

Main Results:

  • The DMQCH/DMQCH-d4 pair demonstrated high derivatization efficiency and a 15-fold increase in MS signal intensity for maltoheptaose.
  • Excellent reproducibility (CV < 13.6%) and linearity (R² > 0.99) were achieved over two orders of magnitude.
  • Successful application in analyzing differential N-glycan profiles in human serum from healthy controls and ovarian cancer patients.

Conclusions:

  • The novel DMQCH/DMQCH-d4 isotopic hydrazide pair offers an efficient and robust method for quantitative glycomics.
  • This technique shows significant potential for biomarker discovery and clinical applications in disease diagnostics.