Minimum structure requirement of immunomodulatory glycolipids for predominant Th2 cytokine induction and the discovery of non-linear phytosphingosine analogs.
Analogs of immunomodulatory glycolipid OCH (2) were prepared and minimum structure requirement to exhibit equivalent profiles was disclosed. Analogs bearing non-linear hydrocarbon chain in the phytosphingosine moiety (18, 19) were shown for the first time to possess comparable cytokine inducing profile to 2. Molecular modeling of 2/hCD1d complex based on the crystal structure of alpha-GalCer (1)/hCD1d complex is also described.
Toba
Tetsuya
T
Biomedical Research Laboratories, Daiichi Asubio Pharma Co., Ltd, Japan.
Murata
Kenji
K
Nakanishi
Kyoko
K
Takahashi
Bitoku
B
Takemoto
Naohiro
N
Akabane
Minako
M
Nakatsuka
Takashi
T
Imajo
Seiichi
S
Yamamura
Takashi
T
Miyake
Sachiko
S
Annoura
Hirokazu
H
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D015394:Molecular Structure; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; D006017:Glycolipids; D007155:Immunologic Factors; C012491:phytosphingosine; D013110:Sphingosine