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Glycan Sequence-Dependent Nod2 Activation Investigated by Using a Chemically Synthesized Bacterial Peptidoglycan Fragment Library

Authors

  • Ning Wang,

    1. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan)
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  • Dr. Cheng-yuan Huang,

    1. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan)
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  • Dr. Mizuho Hasegawa,

    1. Department of Pathology, University of Michigan Medical School, 1150 W. Medical Center Dr., Ann Arbor, Michigan 48109 (USA)
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  • Prof. Dr. Naohiro Inohara,

    1. Department of Pathology, University of Michigan Medical School, 1150 W. Medical Center Dr., Ann Arbor, Michigan 48109 (USA)
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  • Prof. Dr. Yukari Fujimoto,

    Corresponding author
    1. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan)
    • Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan)
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  • Prof. Dr. Koichi Fukase

    Corresponding author
    1. Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan)
    • Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan)
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Abstract

Nucleotide oligomerization domain-containing protein 2 (Nod2), an innate immune receptor, recognizes bacterial cell-wall peptidoglycan (PGN), the minimum ligand of which is muramyl dipeptide (MDP). Enzymatic digestion of PGN appears to be important for Nod2 recognition. PGN is degraded by muramidase or glucosamidase through a process that produces two types of glycan sequence; glycans containing GlcNAcβ(1→4)MurNAc or MurNAcβ(1→4)GlcNAc. In this report, a range of disaccharide or tetrasaccharide fragments of each sequence were chemically synthesized, and their activities in stimulating human Nod2 (hNod2) were investigated. The results reveal that hNod2 recognitions is dependent on the glycan sequence, as demonstrated by comparing the activities of glycans with the same peptide moieties. (MurNAcβ(1→4)GlcNAc)2-containing structures exhibited stronger activity than those containing (GlcNAcβ(1→4)MurNAc)2. The results suggest that differences in the enzymatic degradation process affect the host's immunomodulation process.

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