Chemical synthesis of peptidoglycan fragments for elucidation of the immunostimulating mechanism.
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.
Fujimoto
Yukari
Y
Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan.
Inamura
Seiichi
S
Kawasaki
Akiko
A
Shiokawa
Zenyu
Z
Shimoyama
Atsushi
A
Hashimoto
Takashi
T
Kusumoto
Shoichi
S
Fukase
Koichi
K
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
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