title: Synthesis and biological evaluation of α-galactosylceramide analogues with heteroaromatic rings and varying positions of a phenyl group in the sphingosine backbone.
abstract: We designed and synthesized seven α-GalCer analogues with a pyrazole moiety and varying positions of a phenyl group in the sphingosine backbone to polarize cytokine secretion. On the basis of in vitro and in vivo biological evaluations, we found that analogue 5 induced greater polarization toward Th2 and greater secretion of the immunomodulatory cytokine, IL-4, over secretion of pro-inflammatory cytokines, IFN-γ and IL-17. Treatment of a single dose of analogue 5 markedly ameliorated disease pathogenesis in an animal model of an inflammatory demyelinating disease of the central nervous system, compared to that of KRN7000 (1). Therefore, this new α-GalCer analogue 5 is a novel iNKT ligand that stimulates the selective secretion of anti-inflammatory cytokines and regulates autoimmune diseases by reducing Th1 and Th17 responses.
authors.affiliation: Department of Chemistry, Seoul National University , Seoul 151-747, Korea.
authors.forename: Yongju
authors.initials: Y
authors.lastname: Kim
authors.forename: Keunhee
authors.initials: K
authors.lastname: Oh
authors.forename: Heebum
authors.initials: H
authors.lastname: Song
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.forename: Seung Bum
authors.initials: SB
authors.lastname: Park
mesh_terms: D000818:Animals; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D021241:Spectrometry, Mass, Electrospray Ionization; D013110:Sphingosine / Q000737:chemistry*
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D013110:Sphingosine