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

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10318-10330
Number of pages13
JournalChemistry - A European Journal
Volume14
Issue number33
DOIs
Publication statusPublished - 2008 Nov 17
Externally publishedYes

Keywords

  • Carbohydrates
  • Immunochemistry
  • Peptides
  • Tracheal cytotoxin

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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