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Microwave-Assisted Solid-Phase Synthesis of Antifreeze Glycopeptides

Authors

  • Dr. Ryukou Izumi,

    1. Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021 (Japan)
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  • Dr. Takahiko Matsushita,

    1. Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021 (Japan)
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  • Dr. Naoki Fujitani,

    1. Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021 (Japan)
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  • Dr. Kentaro Naruchi,

    1. Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021 (Japan)
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  • Dr. Hiroki Shimizu,

    1. National Institute of Advanced Industrial Science and Technology, Sapporo, 062-8517 (Japan)
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  • Dr. Sakae Tsuda,

    1. National Institute of Advanced Industrial Science and Technology, Sapporo, 062-8517 (Japan)
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  • Dr. Hiroshi Hinou,

    1. Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021 (Japan)
    2. Medicinal Chemistry Pharmaceuticals, Co., Ltd. N21, W12, Kita-ku, Sapporo 001-0021 (Japan)
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  • Prof. Dr. Shin-Ichiro Nishimura

    Corresponding author
    1. Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021 (Japan)
    2. Medicinal Chemistry Pharmaceuticals, Co., Ltd. N21, W12, Kita-ku, Sapporo 001-0021 (Japan)
    • Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021 (Japan)
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Abstract

Microwave-assisted solid-phase synthesis allows for the rapid and large-scale preparation and structure–activity characterization of tandem repeating glycopeptides, namely monodispersed synthetic antifreeze glycopeptides (syAFGPs, H-[Ala-Thr(Galβ1,3GalNAcα1→)-Ala]n-OH, n=2–6). By employing novel AFGP analogues, we have demonstrated that of the monodispersed syAFGPn (n=2–6, degree of polymerization, DP=2–6, Mw=1257–3690 Da), syAFGP5 (DP=5, Mw=3082 Da) and syAFGP6 (DP=6, Mw=3690 Da) exhibit the ability to form typical hexagonal bipyramidal ice crystals and satisfactory thermal hysteresis activity. Structural characterization by NMR and CD spectroscopy revealed that syAFGP6 forms a typical poly-L-proline type II helix-like structure in aqueous solution whereas enzymatic modification by sialic acid of the residues at the C-3 positions of the nonreducing Gal residues disturbs this conformation and eliminates the antifreeze activity.

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