Synthesis of RCAI-172 (C6 epimer of RCAI-147) and its biological activity |
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| Institution: | 1. Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan;2. Advanced Science Institute, RIKEN, Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan;3. 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;1. RIKEN, Wako-shi, Saitama 351-0198, Japan;2. Department of Nutritional Science, Faculty of Applied Bio-Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan;1. RIKEN, Wako-shi, Saitama 351-0198, Japan;2. Division of Material Science, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan;3. The United Graduate School of Agricultural Sciences, Iwate University, Morioka, Iwate 020-8550, Japan;1. Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 305-806, Republic of Korea;2. Global Research Cluster, RIKEN, Hirosawa 2-1, Wako, Saitama 351-0198, Japan;3. Division of Magnetic Resonance Research, Korea Basic Science Institute, 162 Ochang, Cheongwongun, Chungbuk, Republic of Korea;1. Chemical Biology Laboratory, Graduate School of Arts and Sciences, Iwate University, Morioka 020-8550, Japan;2. Hiroshima Research Center for Healthy Aging, Hiroshima University, Higashi-Hiroshima 739-8530, Japan;3. Division of Biological and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8530, Japan;4. RIKEN Center for Sustainable Resource Science, Wako 351-0198, Japan;5. Department of Biological Chemistry and Food Science, Iwate University, Morioka 020-8550, Japan;1. Department of Bioscience, Tokyo University of Agriculture, Tokyo 156-8502, Japan;2. Department of Nutritional Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan;3. Department of Fermentation Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan;4. Chemical Biology Department, RIKEN Advance Science Institute, Saitama 351-0198, Japan;1. Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, United States;2. RIKEN Center for Sustainable Resource Science, Saitama 351-0198, Japan;3. Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, United States |
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| 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. |
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| Keywords: | Glycolipids Glycosylation KRN7000 iNKT cells Th1/Th2 EAE |
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