20 自然免疫を活性化する細菌細胞壁ペプチドグリカン・フラグメントの構造解析,合成と機能(口頭発表の部)
書誌事項
- タイトル別名
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- Innate Immunostimulating Bacterial Cell Wall Peptidoglycan : Structure Elucidation of Fragments in Environment, Their Chemical Synthesis, and Bioimmunological Functions
説明
Bacterial cell wall peptidoglycan (PGN) is a potent immunopotentiater and an adjuvant for antibody production. We have recently revealed that intracellular proteins, Nod1 and Nod2, are innate immune receptors of PGN, which recognize diaminopimelic acid (DAP) containing peptide components and muramyldipeptide (MDP) respectively, using synthesized PGN partial structures. We have also revealed that DAP-type PGN containing bacteria release Nod1 ligands to the environments. Genetic studies have shown that polymorphsms in human NOD1 gene significantly associated with susceptibility to several diseases including allergic deseases such as asthma. However, the function and the immunostimulating mechanism of Nod1 have not yet been well understood. We thus analyzed the PGN fragments released to the environment, and synthesized DAP-type PGN fragments including tracheal cytotoxin (TCT). Based on the preparation strategy of the β(1→4) glycans using appropriately protected GlcNTroc and MurNTroc (or MurNTroc(anh)), and a newly developed synthetic method of DAP, we achieved the first chemical synthesis of TCT and a repeating unit of DAP-type PGN fragment. We also synthesized a series of the partial structures, and observed human-Nod1 stimulation activities. The results demonstrated that the glycan partof the ligands enhance the Nod1 activation. We also prepared a library of γ-D-glutamyl-DAP(iE-DAP) derivatives and found N-myristoyl-iE-DAP as a stronger Nod1 activator. The compound enabled us to investigate Nod1 function in vivo.
収録刊行物
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- 天然有機化合物討論会講演要旨集
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天然有機化合物討論会講演要旨集 51 (0), 115-120, 2009
天然有機化合物討論会実行委員会
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詳細情報 詳細情報について
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- CRID
- 1390282681055013888
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- NII論文ID
- 110009757627
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- ISSN
- 24331856
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可
