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Human Milk Oligosaccharide Specificities of Human Galectins. Comparison of Electrospray Ionization Mass Spectrometry and Glycan Microarray Screening Results
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    Human Milk Oligosaccharide Specificities of Human Galectins. Comparison of Electrospray Ionization Mass Spectrometry and Glycan Microarray Screening Results
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    Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta Canada T6G 2G2
    INRS-Institut Armand-Frappier, Laval, Québec Canada H7 V 1B7
    *E-mail: [email protected]. Telephone: (780) 492-3501. Fax: (780) 492 8231.
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    Analytical Chemistry

    Cite this: Anal. Chem. 2017, 89, 9, 4914–4921
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    https://doi.org/10.1021/acs.analchem.6b05169
    Published March 27, 2017
    Copyright © 2017 American Chemical Society

    Abstract

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    The affinities of thirty-two free human milk oligosaccharides (HMOs) for four human galectin proteins, a stable mutant of hGal1 (hGal-1), a C-terminal fragment of hGal-3 (hGal-3C), hGal-7, and an N-terminal fragment of hGal-9 (hGal-9N), were measured using electrospray ionization mass spectrometry (ESI-MS). The binding data show that each of the four galectins recognize the majority of the HMOs tested (hGal-1 binds thirty-two HMOs, hGal-3C binds twenty-six, hGal-7 binds thirty-one, and hGal-9N binds twenty-six). Twenty-five of the HMOs tested bind all four galectins, with affinities ranging from 103 to 105 M–1. The reliability of the ESI-MS assay for quantifying the affinities of HMOs for lectins was established from the agreement found between the ESI-MS data and affinities of a small number of HMOs for hGal-1, hGal-3C, and hGal-7 measured by isothermal titration calorimetry (ITC). Comparison of the relative affinities (of 14 HMOs) measured by ESI-MS with the reported specificities of hGal-1, hGal-3, hGal-7, and hGal-9 for these same HMOs established using the shotgun human milk glycan microarray (HM-SGM-v2) showed fair-to-poor correlation, with evidence of false positives and false negatives in the microarray data. The results of this study suggest that HMO specificities of lectins established using microarrays may not accurately reflect their true HMO-binding properties and that the use of “in solution” assays such as ESI-MS and ITC is to be preferred.

    Copyright © 2017 American Chemical Society

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.6b05169.

    • Experimental details, affinities, HMOs structures and purities, mass spectra, ITC data, comparison of affinities and RFU values, synthesis of “open-ring” and “closed-ring” conjugates (PDF)

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    36. Vassilis Triantis, Lars Bode, R. J. Joost van Neerven. Immunological Effects of Human Milk Oligosaccharides. Frontiers in Pediatrics 2018, 6 https://doi.org/10.3389/fped.2018.00190
    37. Amr El-Hawiet, Yajie Chen, Km Shams-Ud-Doha, Elena N. Kitova, Pavel I. Kitov, Lars Bode, Naim Hage, Franco H. Falcone, John S. Klassen. Screening natural libraries of human milk oligosaccharides against lectins using CaR-ESI-MS. The Analyst 2018, 143 (2) , 536-548. https://doi.org/10.1039/C7AN01397C
    38. Tadasu Urashima, Jun Hirabayashi, Sachiko Sato, Akira Kobata. Human Milk Oligosaccharides as Essential Tools for Basic and Application Studies on Galectins. Trends in Glycoscience and Glycotechnology 2018, 30 (172) , SE51-SE65. https://doi.org/10.4052/tigg.1734.1SE
    39. Tadasu Urashima, Jun Hirabayashi, Sachiko Sato, Akira Kobata. Human Milk Oligosaccharides as Essential Tools for Basic and Application Studies on Galectins. Trends in Glycoscience and Glycotechnology 2018, 30 (172) , SJ11-SJ24. https://doi.org/10.4052/tigg.1734.1SJ
    40. Esther H. Yang, Julia Rode, Md. Amran Howlader, Marina Eckermann, Jobette T. Santos, Daniel Hernandez Armada, Ruixiang Zheng, Chunxia Zou, Christopher W. Cairo, . Galectin-3 alters the lateral mobility and clustering of β1-integrin receptors. PLOS ONE 2017, 12 (10) , e0184378. https://doi.org/10.1371/journal.pone.0184378

    Analytical Chemistry

    Cite this: Anal. Chem. 2017, 89, 9, 4914–4921
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.6b05169
    Published March 27, 2017
    Copyright © 2017 American Chemical Society

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