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ID 55449
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Vavrick, Christopher J. Graduate School of Environmental and Life Science, Okayama University
Muto, Chiaki Graduate School of Environmental and Life Science, Okayama University
Hasunuma, Tomohisa Graduate School of Science, Technology and Innovation, Kobe University
Kimura, Yoshinobu Graduate School of Environmental and Life Science, Okayama University
Araki, Michihiro Graduate School of Science, Technology and Innovation, Kobe University
Wu, Yan CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Gao, George F. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Ohrui, Hiroshi Yokohama College of Pharmacy
Izumi, Minoru Graduate School of Environmental and Life Science, Okayama University
Kiyota, Hiromasa Graduate School of Environmental and Life Science, Okayama University
Abstract
The design, synthesis and application of N-acetylneuraminic acid-derived compounds bearing anomeric sulfo functional groups are described. These novel compounds, which we refer to as sulfo-sialic acid analogues, include 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid and its 4-deoxy-3,4-dehydrogenated pseudoglycal. While 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid contains no further modifications of the 2-deoxy-pyranose ring, it is still a more potent inhibitor of avian-origin H5N1 neuraminidase (NA) and drug-resistant His275Tyr NA as compared to the oxocarbenium ion transition state analogue 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. The sulfo-sialic acid analogues described in this report are also more potent inhibitors of influenza NA (up to 40-fold) and bacterial NA (up to 8.5-fold) relative to the corresponding anomeric phosphonic acids. These results confirm that this novel anomeric sulfo modification offers great potential to improve the potency of next-generation NA inhibitors including covalent inhibitors.
Note
This is an article published by Science
Published Date
2017-08
Publication Title
Scientific Reports
Volume
volume7
Issue
issue1
Publisher
Nature Publishing Group
Start Page
8239
ISSN
2045-2322
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
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Related Url
https://doi.org/10.1038/s41598-017-07836-y