4.8 Article

Enhanced Detection of Charged N-Glycans in the Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometric Imaging

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ANALYTICAL CHEMISTRY
卷 95, 期 29, 页码 10913-10920

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AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.3c00494

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N-linked glycosylation is a complex protein modification that plays a role in cellular signaling and metabolism. Aberrant protein glycosylation is a characteristic feature of many diseases. Spatial profiling of N-glycans through imaging on tissue sections can be used for disease diagnosis. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is a sensitive technique that can be used for mass spectrometry imaging.
N-linked glycosylationrepresents astructurallydiverse, complex, co- and posttranslational protein modification thatbridges metabolism and cellular signaling. Consequently, aberrantprotein glycosylation is a hallmark of most pathological scenarios.Due to their complex nature and non-template-driven synthesis, theanalysis of glycans is faced with several challenges, underliningthe need for new and improved analytical technologies. Spatial profilingof N-glycans through direct imaging on tissue sectionsreveals the regio-specific and/or disease pathology correlating tissue N-glycans that serve as a disease glycoprint for diagnosis.Infrared matrix-assisted laser desorption electrospray ionization(IR-MALDESI) is a soft hybrid ionization technique that has been usedfor diverse mass spectrometry imaging (MSI) applications. Here, wereport the first spatial analysis of the brain N-linkedglycans by IR-MALDESI MSI, leading to a significant increase in thedetection of the brain N-sialoglycans. A formalin-fixedparaffin-embedded mouse brain tissue was analyzed in negative ionizationmode after tissue washing, antigen retrieval, and pneumatic applicationof PNGase F for enzymatic digestion of N-linked glycans.We report a comparative analysis of section thickness on the N-glycan detection using IR-MALDESI. One hundred thirty-sixunique N-linked glycans were confidently identifiedin the brain tissue (with an additional 132 unique N-glycans, not reported in GlyConnect), where more than 50% containedsialic acid residues, which is approximately 3-fold higher than theprevious reports. This work demonstrates the first application ofIR-MALDESI in N-linked glycan imaging of the braintissue, leading to a 2.5-fold increase in the in situ total brain N-glycan detection compared to the current gold standardof positive-mode matrix-assisted laser desorption/ionization massspectrometry imaging. This is also the first report of the applicationof the MSI toward the identification of sulfoglycans in the rodentbrain. Overall, IR-MALDESI-MSI presents a sensitive glycan detectionplatform to identify tissue-specific and/or disease-specific glycosignaturein the brain while preserving the sialoglycans without any chemicalderivatization.

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