title: Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3).
abstract: Glycoceramides can activate NKT cells by binding with CD1d to produce IFN-gamma, IL-4, and other cytokines. An efficient synthetic pathway for alpha-galactosylceramide (KRN7000) was established by coupling a protected galactose donor to a properly protected ceramide. During the investigation, it was discovered that when the ceramide was protected with benzyl groups, only beta-galactosylceramide was produced from the glycosylation reaction. In contrast, the ceramide with benzoyl protecting groups produced alpha-galactosylceramide. Isoglobotrihexosylceramide (iGb3) was prepared by glycosylation of Galalpha1-3Galbeta1-4Glc donor with 2-azido-sphingosine in high yield. Biological assays on the synthetic KRN7000 and iGb3 were performed using human and murine iNKT cell clones or hybridomas.
authors.affiliation: Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Xia
authors.forename: Qingjia
authors.initials: Q
authors.lastname: Yao
authors.forename: Jens
authors.initials: J
authors.lastname: Schümann
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rossy
authors.forename: Wenlan
authors.initials: W
authors.lastname: Chen
authors.forename: Lizhi
authors.initials: L
authors.lastname: Zhu
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.forename: Peng George
authors.initials: PG
authors.lastname: Wang
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000494:pharmacology*; D005915:Globosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D014162:Transfection
chemical_list: D018949:Antigens, CD1; D016207:Cytokines; D005699:Galactosylceramides; D005915:Globosides; D015847:Interleukin-4; D007371:Interferon-gamma; C037097:isoglobotriaosylceramide; C103873:KRN 7000