Synthesis and Th1-immunostimulatory activity of α-galactosylceramide analogues bearing a halogen-containing or selenium-containing acyl chain.
A novel series of CD1d ligand α-galactosylceramides (α-GalCers) were synthesized by incorporation of the heavy atoms Br and Se in the acyl chain backbone of α-galactosyl-N-cerotoylphytosphingosine. The synthetic analogues are potent CD1d ligands and stimulate mouse invariant natural killer T (iNKT) cells to selectively enhance Th1 cytokine production. These synthetic analogues would be efficient X-ray crystallographic probes to disclose precise atomic positions of alkyl carbons and lipid-protein interactions in KRN7000/CD1d complexes.
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan; JST, ERATO, Lipid Active Structure Project, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Md Imran
MI
Hossain
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan. Electronic address: hanashimas13@chem.sci.osaka-u.ac.jp.
Shinya
S
Hanashima
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Takuto
T
Nomura
JST, ERATO, Lipid Active Structure Project, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Sébastien
S
Lethu
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Hiroshi
H
Tsuchikawa
Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan; JST, ERATO, Lipid Active Structure Project, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan. Electronic address: murata@chem.sci.osaka-u.ac.jp.
Michio
M
Murata
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Hiroki
H
Kusaka
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Shunsuke
S
Kita
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Katsumi
K
Maenaka
D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005699:Galactosylceramides / Q000737:chemistry / Q000494:pharmacology*; D006219:Halogens / Q000737:chemistry*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D066244:Proton Magnetic Resonance Spectroscopy; D012643:Selenium / Q000737:chemistry*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D005699:Galactosylceramides; D006219:Halogens; C493154:alpha-galactosylceramide; D012643:Selenium
CD1d; Cytokines; Glycosylation; Natural product synthesis; α-GalCer