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

抄録

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.

収録刊行物

• Scientific Reports

  Scientific Reports (7), 8239-, 2017-08-15

  Nature Publishing Group

詳細情報

• CRID: 1570572702830893440
• NII論文ID: 120006352247
• ISSN: 20452322
• Web Site: http://www.lib.kobe-u.ac.jp/handle_kernel/90004200
• 本文言語コード: en
• データソース種別:
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