Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3).
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.
Xia
Chengfeng
C
Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Yao
Qingjia
Q
Schümann
Jens
J
Rossy
Emmanuel
E
Chen
Wenlan
W
Zhu
Lizhi
L
Zhang
Wenpeng
W
De Libero
Gennaro
G
Wang
Peng George
PG
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
D018949:Antigens, CD1; D016207:Cytokines; D005699:Galactosylceramides; D005915:Globosides; D015847:Interleukin-4; D007371:Interferon-gamma; C037097:isoglobotriaosylceramide; C103873:KRN 7000