Minimum structure requirement of immunomodulatory glycolipids for predominant Th2 cytokine induction and the discovery of non-linear phytosphingosine analogs

Tetsuya Toba; Kenji Murata; Kyoko Nakanishi; Bitoku Takahashi; Naohiro Takemoto; Minako Akabane; Takashi Nakatsuka; Seiichi Imajo; Takashi Yamamura; Sachiko Miyake; Hirokazu Annoura

doi:10.1016/j.bmcl.2007.02.081

Minimum structure requirement of immunomodulatory glycolipids for predominant Th2 cytokine induction and the discovery of non-linear phytosphingosine analogs

Bioorg Med Chem Lett. 2007 May 15;17(10):2781-4. doi: 10.1016/j.bmcl.2007.02.081. Epub 2007 Mar 3.

Authors

Tetsuya Toba¹, Kenji Murata, Kyoko Nakanishi, Bitoku Takahashi, Naohiro Takemoto, Minako Akabane, Takashi Nakatsuka, Seiichi Imajo, Takashi Yamamura, Sachiko Miyake, Hirokazu Annoura

Affiliation

¹ Biomedical Research Laboratories, Daiichi Asubio Pharma Co., Ltd, Japan.

PMID: 17419054
DOI: 10.1016/j.bmcl.2007.02.081

Abstract

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.

MeSH terms

Animals
Cytokines / metabolism*
Glycolipids / metabolism*
Humans
Immunologic Factors / metabolism*
Molecular Structure
Sphingosine / analogs & derivatives*
Sphingosine / chemistry
Th2 Cells / metabolism*

Substances

Cytokines
Glycolipids
Immunologic Factors
phytosphingosine
Sphingosine