start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=8239 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality en-subtitle= kn-subtitle= en-abstract= kn-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. en-copyright= kn-copyright= en-aut-name=VavrickChristopher J. en-aut-sei=Vavrick en-aut-mei=Christopher J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MutoChiaki en-aut-sei=Muto en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasunumaTomohisa en-aut-sei=Hasunuma en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraYoshinobu en-aut-sei=Kimura en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ArakiMichihiro en-aut-sei=Araki en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WuYan en-aut-sei=Wu en-aut-mei=Yan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GaoGeorge F. en-aut-sei=Gao en-aut-mei=George F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhruiHiroshi en-aut-sei=Ohrui en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiMinoru en-aut-sei=Izumi en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KiyotaHiromasa en-aut-sei=Kiyota en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Science, Technology and Innovation, Kobe University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Science, Technology and Innovation, Kobe University kn-affil= affil-num=6 en-affil=CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=Yokohama College of Pharmacy kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=7 cd-vols= no-issue=1 article-no= start-page=8239 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=201708 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality en-subtitle= kn-subtitle= en-abstract= kn-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. en-copyright= kn-copyright= en-aut-name=VavrickaChristopher J. en-aut-sei=Vavricka en-aut-mei=Christopher J. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MutoChiaki en-aut-sei=Muto en-aut-mei=Chiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HasunumaTomohisa en-aut-sei=Hasunuma en-aut-mei=Tomohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KimuraYoshinobu en-aut-sei=Kimura en-aut-mei=Yoshinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ArakiMichihiro en-aut-sei=Araki en-aut-mei=Michihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WuYan en-aut-sei=Wu en-aut-mei=Yan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=GaoGeorge F. en-aut-sei=Gao en-aut-mei=George F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhruiHiroshi en-aut-sei=Ohrui en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IzumiMinoru en-aut-sei=Izumi en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KiyotaHiromasa en-aut-sei=Kiyota en-aut-mei=Hiromasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Science, Technology and Innovation, Kobe University kn-affil= affil-num=4 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Science, Technology and Innovation, Kobe University kn-affil= affil-num=6 en-affil=CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences kn-affil= affil-num=7 en-affil=CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences kn-affil= affil-num=8 en-affil=Yokohama College of Pharmacy kn-affil= affil-num=9 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= affil-num=10 en-affil=Graduate School of Environmental and Life Science, Okayama University kn-affil= en-keyword=Antiviral agents kn-keyword=Antiviral agents en-keyword=Drug discovery and development kn-keyword=Drug discovery and development en-keyword=Glycosides kn-keyword=Glycosides END