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

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...

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Autores principales:	Christopher J. Vavricka, Chiaki Muto, Tomohisa Hasunuma, Yoshinobu Kimura, Michihiro Araki, Yan Wu, George F. Gao, Hiroshi Ohrui, Minoru Izumi, Hiromasa Kiyota
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d71999dbcf09495f926bec89b3dbfc54
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spelling	oai:doaj.org-article:d71999dbcf09495f926bec89b3dbfc542021-12-02T12:32:24ZSynthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality10.1038/s41598-017-07836-y2045-2322https://doaj.org/article/d71999dbcf09495f926bec89b3dbfc542017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07836-yhttps://doaj.org/toc/2045-2322Abstract 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.Christopher J. VavrickaChiaki MutoTomohisa HasunumaYoshinobu KimuraMichihiro ArakiYan WuGeorge F. GaoHiroshi OhruiMinoru IzumiHiromasa KiyotaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher J. Vavricka Chiaki Muto Tomohisa Hasunuma Yoshinobu Kimura Michihiro Araki Yan Wu George F. Gao Hiroshi Ohrui Minoru Izumi Hiromasa Kiyota Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
description	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.
format	article
author	Christopher J. Vavricka Chiaki Muto Tomohisa Hasunuma Yoshinobu Kimura Michihiro Araki Yan Wu George F. Gao Hiroshi Ohrui Minoru Izumi Hiromasa Kiyota
author_facet	Christopher J. Vavricka Chiaki Muto Tomohisa Hasunuma Yoshinobu Kimura Michihiro Araki Yan Wu George F. Gao Hiroshi Ohrui Minoru Izumi Hiromasa Kiyota
author_sort	Christopher J. Vavricka
title	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_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_sort	synthesis of sulfo-sialic acid analogues: potent neuraminidase inhibitors in regards to anomeric functionality
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d71999dbcf09495f926bec89b3dbfc54
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Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality

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