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Site-Specific Introduction of Sialic Acid into Insulin

Authors

  • Masaaki Sato,

    1. Division of Biological Sciences, Graduate School of Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan, Fax: (+81) 11-706-9042
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  • Reiko Sadamoto Dr.,

    1. Shionogi Laboratory of Biomolecular Chemistry, Division of Biological Science, Graduate School of Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan
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  • Kenichi Niikura Dr.,

    1. Division of Biological Sciences, Graduate School of Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan, Fax: (+81) 11-706-9042
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  • Kenji Monde Dr.,

    1. Division of Biological Sciences, Graduate School of Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan, Fax: (+81) 11-706-9042
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  • Hirosato Kondo Dr.,

    1. Discovery Research Laboratories, Shionogi & Co., Ltd., Osaka 553-0002, Japan
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  • Shin-Ichiro Nishimura Prof.

    1. Division of Biological Sciences, Graduate School of Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan, Fax: (+81) 11-706-9042
    2. Japan Bioindustry Association, Sapporo 060-0810, Japan
    3. National Insutitute of Advanced Industrial Science and Technology (AIST), Sapporo 062-8517, Japan
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  • This work was supported partly by a grant for “Research and Development on Glycocluster Controlling Biomolecules” from the New Energy and Industrial Technology Development Organization (NEDO). M.S. would like to thank Mr. A. Toda, Dr. K. Yamada, Dr. K. Iwata, Mr. T. Ohta, and Dr. H. Nakagawa for helpful discussions.

Abstract

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Ein neues Insulin mit langer Wirkdauer (siehe Struktur) wurde durch enzymatischen Einbau von Sialyllactose in Insulinmutanten hergestellt. Die Glycosylierungsstelle wurde ohne Verlust biologischer Aktivität durch Punktmutation in das Insulin eingeführt. Die Experimente am Mausmodell zeigen deutlich, dass der Sialinsäurerest entscheidend für eine verlängerte Blutglucose regulierende Wirkung ist.

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