title: Chemical synthesis of peptidoglycan fragments for elucidation of the immunostimulating mechanism.
abstract: Partial structures of peptidoglycan were chemically synthesized for elucidation of their precise biological activities. By using an efficient synthetic strategy, mono-, di-, tetra- and octasaccharide fragments of peptidoglycan were synthesized in good yields. The biological activity of synthetic fragments of peptidoglycan was evaluated by induction of TNF-alpha from human monocytes, and TLR2 and NOD2 dependencies by using transfected HEK293 cells, respectively. We revealed that TLR2 was not stimulated by the series of synthetic peptidoglycan partial structures, whereas NOD2 recognizes the partial structures containing the MDP moiety. We also synthesized potent NOD1 agonists, which showed several hundred-fold stronger activity than gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP). Interaction of PGRPs with synthetic peptidoglycan fragments is also described.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Seiichi
authors.initials: S
authors.lastname: Inamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Zenyu
authors.initials: Z
authors.lastname: Shiokawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimoyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
mesh_terms: D002460:Cell Line; D006801:Humans; D015394:Molecular Structure; D009000:Monocytes / Q000737:chemistry; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology*; D010457:Peptidoglycan / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010446:Peptide Fragments; D010457:Peptidoglycan; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha