Self and nonself recognition with bacterial and animal glycans, surveys by synthetic chemistry

Yukari Fujimoto, Katsunori Tanaka, Atsushi Shimoyama, Koichi Fukase

研究成果: Chapter

6 被引用数 (Scopus)

抄録

In this chapter, we describe synthetic studies on partial structures of lipopolysaccharide (LPS) and peptidoglycan (PGN), which work as tags for nonself recognition in innate immune system. Our previous studies demonstrated that lipid A is the endotoxic principle of LPS. The synthetic homogeneous preparations have enabled not only precise structure-activity relationships, but also recognition mechanisms of LPS with innate immune receptor complexes, including the TLR4/MD-2 complex, to be studied. Synthetic studies of lipid A and Kdo-lipid A from parasitic Helicobacter pylori revealed their low inflammatory activities, suggesting the molecular evolution to escape from the host immune system. A synthetic study of the partial structures of PGN has also contributed to the understanding of the innate immune mechanism. The biological activities of the synthetic fragments have revealed that the intracellular receptor Nod2 recognizes partial structures containing the muramyl dipeptide (MDP) moiety. The PGN of Gram-negative bacteria and some Gram-positive bacteria contain meso-diaminopimelic acid (meso-DAP), and recent studies have revealed that the intracellular receptor Nod1 recognizes DAP-containing peptides. We have synthesized DAP-containing PGN fragments, including the first chemical synthesis of tracheal cytotoxin (TCT). The ability of these fragments to stimulate human Nod1 as well as differences in Nod1 recognition for various synthesized ligand structures was elucidated. Cell-surface glycans such as N-glycans and O-glycans on glycoproteins and glycoconjugates work as signaling molecules for self-recognition and control immune system. Our new strategy using glycan-imaging in whole-body system is expected to unveil the dynamics of glycans in the body. Positron emission tomography (PET) is a noninvasive method that visualizes the locations and levels of radiotracer accumulation. We developed the facile labeling of peptides and proteins for PET imaging. The labeled glycoproteins and glycoclusters were then subjected to PET imaging in order to examine their in vivo dynamics, visualizing the differences in the circulatory residence of glycoproteins and glycoclusters in the presence or absence of sialic acid residues.

本文言語English
ホスト出版物のタイトルMethods in Enzymology
出版社Academic Press Inc.
ページ323-342
ページ数20
C
DOI
出版ステータスPublished - 2010
外部発表はい

出版物シリーズ

名前Methods in Enzymology
番号C
478
ISSN(印刷版)0076-6879

ASJC Scopus subject areas

  • 生化学
  • 分子生物学

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