Synthesis of diaminopimelic acid containing peptidoglycan fragments and tracheal cytotoxin (TCT) and investigation of their biological functions

Akiko Kawasaki, Yukie Karasudani, Yuji Otsuka, Mizuho Hasegawa, Naohiro Inohara, Yukari Fujimoto, Koichi Fukase

研究成果: Article査読

43 被引用数 (Scopus)

抄録

Bacterial cell wall peptidoglycan (PGN) is a potent immunostimulator and immune adjuvant. The PGN of Gram-negative bacteria and some Gram-positive bacteria contain meso-diaminopimelic acid (meso-DAP), and we have recently shown that the intracellular protein Nodi is a PGN receptor and recognizes DAPcontaining peptides. In this study, we achieved the synthesis of DAP-containing PGN fragments, including the first chemical synthesis of tracheal cytotoxin (TCT), GlcNAc-(β1-4)-(anhydro) Mur-NAc-L-Ala-γ-D-Glu-meso- DAP-D-Ala, and a repeating-unit of DAP-type PGN, GlcNAc-(β1-4)-MurNAc-L- Ala-γ-D-Glu-meso-DAP-D-Ala. For the synthesis of PGN fragments, we first established a new synthetic method for an orthogonally protected meso-DAP derivative, and then we constructed the glycopeptide structures. The ability of these fragments to stimulate human Nodi, as well as differences in Nodi recognition of the variety of synthesized ligand structures were examined. The results showed that the substitution of the N terminus of iE-DAP is necessary for stronger Nodi recognition, but the structure of the substituent seems not to be strictly recognized. The importance of the carboxyl group at the 2-position of DAP for human Nod1 stimulation was also shown.

本文言語English
ページ(範囲)10318-10330
ページ数13
ジャーナルChemistry - A European Journal
14
33
DOI
出版ステータスPublished - 2008 11 17
外部発表はい

ASJC Scopus subject areas

  • 触媒
  • 有機化学

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