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Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality

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-dehydrog...

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Autores principales: Vavricka, Christopher J., Muto, Chiaki, Hasunuma, Tomohisa, Kimura, Yoshinobu, Araki, Michihiro, Wu, Yan, Gao, George F., Ohrui, Hiroshi, Izumi, Minoru, Kiyota, Hiromasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557986/
https://www.ncbi.nlm.nih.gov/pubmed/28811524
http://dx.doi.org/10.1038/s41598-017-07836-y
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author Vavricka, Christopher J.
Muto, Chiaki
Hasunuma, Tomohisa
Kimura, Yoshinobu
Araki, Michihiro
Wu, Yan
Gao, George F.
Ohrui, Hiroshi
Izumi, Minoru
Kiyota, Hiromasa
author_facet Vavricka, Christopher J.
Muto, Chiaki
Hasunuma, Tomohisa
Kimura, Yoshinobu
Araki, Michihiro
Wu, Yan
Gao, George F.
Ohrui, Hiroshi
Izumi, Minoru
Kiyota, Hiromasa
author_sort Vavricka, Christopher J.
collection PubMed
description 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.
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spelling pubmed-55579862017-08-18 Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality Vavricka, Christopher J. Muto, Chiaki Hasunuma, Tomohisa Kimura, Yoshinobu Araki, Michihiro Wu, Yan Gao, George F. Ohrui, Hiroshi Izumi, Minoru Kiyota, Hiromasa Sci Rep Article 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. Nature Publishing Group UK 2017-08-15 /pmc/articles/PMC5557986/ /pubmed/28811524 http://dx.doi.org/10.1038/s41598-017-07836-y Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Vavricka, Christopher J.
Muto, Chiaki
Hasunuma, Tomohisa
Kimura, Yoshinobu
Araki, Michihiro
Wu, Yan
Gao, George F.
Ohrui, Hiroshi
Izumi, Minoru
Kiyota, Hiromasa
Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
title Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
title_full Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
title_fullStr Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
title_full_unstemmed Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
title_short Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
title_sort synthesis of sulfo-sialic acid analogues: potent neuraminidase inhibitors in regards to anomeric functionality
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557986/
https://www.ncbi.nlm.nih.gov/pubmed/28811524
http://dx.doi.org/10.1038/s41598-017-07836-y
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