title: Synthesis of peptidoglycan fragments and evaluation of their biological activity.
abstract: The peptidoglycan (PG) bacterial cell wall glycoconjugate has been well known as a strong immunopotentiator. Partial structures of PG were chemically synthesized for elucidation of precise biological activities. Effective construction of distinct repeating glycans of PG was accomplished by the coupling of a key disaccharide glucosaminyl-beta(1-4)-muramic acid unit. Stereoselective glycosylation of disaccharide units was achieved by neighboring group participation of the N-Troc (Troc = 2,2,2-trichloroethoxycarbonyl) group and appropriate reactivity of N-Troc-glucosaminyl trichloroacetimidate. By using an efficient synthetic strategy, mono-, di-, tetra- and octasaccharide fragments of PG were synthesized in high yields. The biological activity of synthetic fragments of PG was evaluated by induction of tumor necrosis factor-alpha (TNF-alpha) from human monocytes, and toll-like receptor 2 (TLR2) and Nod2 dependencies by using transfected HEK293 cells, respectively. Here we reveal that TLR2 was not stimulated by the series of synthetic PG partial structures, whereas Nod2 recognizes the partial structures containing the MDP moiety.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Inamura
authors.forename: Yukari
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Zenyu
authors.initials: Z
authors.lastname: Shiokawa
authors.forename: Eva
authors.initials: E
authors.lastname: Woelk
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.forename: Buko
authors.initials: B
authors.lastname: Lindner
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000737:chemistry; D002460:Cell Line; D002473:Cell Wall / Q000737:chemistry; D006801:Humans; D009000:Monocytes; D053473:Nod2 Signaling Adaptor Protein / Q000187:drug effects; D009844:Oligosaccharides / Q000138:chemical synthesis; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology*; D010457:Peptidoglycan / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D009844:Oligosaccharides; D010446:Peptide Fragments; D010457:Peptidoglycan; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine