title: Synthesis of RCAI-172 (C6 epimer of RCAI-147) and its biological activity.
abstract: RCAI-147 is one of the hydroxylated analogues of KRN7000 which is known as a ligand for the activation of CD1d mediated invariant natural killer T cells (iNKT cells) and releases both T helper 1 (Th1) cytokines such as IFN-γ and T helper 2 (Th2) cytokines such as IL-4. KRN7000 has been anticipated as an antitumor drug or an adjuvant for viral infection such as influenza, because of its strong secretion of IFN-γ. In an interesting twist, it has been obvious in our previous paper that RCAI-147 induces much more Th2 cytokines (IL-4) than Th1 cytokines (IFN-γ) from iNKT cells compared to KRN7000, and shows fairly good result in the experimental autoimmune encephalomyelitis (EAE) test. Therefore, synthesis of RCAI-172 (C6-OH epimer of RCAI-147) was attempted to examine the biological activity. As a result, RCAI-172 was synthesized and its biological activity biased to Th2 response largely compared to that of KRN7000. However, this level decreased to approximately 61% compared to that of RCAI-147. And the clinical score of RCAI-172 for EAE suppression was disappointing. There exist seven chiral centers in the aglycon part of RCAI-172, and even though the change of configuration is just one position (C6-OH), the effect on both Th1/Th2 response and EAE test is fairly large.
authors.affiliation: Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan. Electronic address: shiozaki@rcai.riken.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Shiozaki
authors.affiliation: Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tashiro
authors.affiliation: Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koshino
authors.affiliation: Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
authors.forename: Tomokuni
authors.initials: T
authors.lastname: Shigeura
authors.affiliation: Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watarai
authors.affiliation: Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Yokohama Institute, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mori
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D005699:Galactosylceramides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000378:metabolism
chemical_list: D005699:Galactosylceramides; C000593072:RCAI-172; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: EAE; Glycolipids; Glycosylation; KRN7000; Th1/Th2; iNKT cells