N-Linked Oligosaccharide Processing Enzymes as Molecular Targets for Drug Discovery

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  • Hakamata Wataru
    Division of Organic Chemistry, National Institute of Health Sciences (NIHS)
  • Muroi Makoto
    Antibiotics Laboratory, The Institute of Physical and Chemical Research (RIKEN)
  • Nishio Toshiyuki
    Department of Biological Chemistry, College of Bioresource Sciences, Nihon University
  • Oku Tadatake
    Department of Biological Chemistry, College of Bioresource Sciences, Nihon University
  • Takatsuki Akira
    Department of Materials Chemistry, Faculty of Engineering, Hosei University
  • Osada Hiroyuki
    Antibiotics Laboratory, The Institute of Physical and Chemical Research (RIKEN)
  • Fukuhara Kiyoshi
    Division of Organic Chemistry, National Institute of Health Sciences (NIHS)
  • Okuda Haruhiro
    Division of Organic Chemistry, National Institute of Health Sciences (NIHS)
  • Kurihara Masaaki
    Division of Organic Chemistry, National Institute of Health Sciences (NIHS)

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  • <i>N</i>-結合型糖鎖プロセッシング酵素を分子標的とした創薬

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Abstract

N-Linked oligosaccharide processing enzymes are key enzymes in the biosynthesis of N-linked oligosaccharides. These enzymes are a molecular target for inhibition by anti-viral agents that interfere with the formation of essential glycoproteins required in viral assembly, secretion and infectivity. We think that the molecular recognition of three kinds of glucosidases (family 13 and family 31 α-glucosidases and endoplasmic reticulum glucosidases) are different. Therefore, glycon and aglycon specificity profiling of glucosidases was an important approach for the research of glucosidase inhibitors. We carried out the profiling of glucosidases using small molecules as a probe. Moreover, we designed and synthesized three types of glucosidase inhibitors. These compounds were evaluated with regard to their ability to inhibit glucosidases in vitro, and were also tested in a cell culture system. We found some compounds having glucosidase inhibitory activity and anti-viral activity.

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