Shimamura Michio, Okamoto Naoki, Huang Yi-Ying, Yasuoka Jouji, Morita Kenji, Nishiyama Akira, Amano Yuusuke, Mishina Tadashi
Developmental Immunology Unit, Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
Eur J Med Chem. 2006 May;41(5):569-76. doi: 10.1016/j.ejmech.2005.11.013. Epub 2006 Mar 20.
A 2-substituted 2-aminopropane-1,3-diol or 2-aminoethanol is the minimum structure required for the immunosuppressive activity of ISP-I, an antibiotic isolated from the culture broth of Isaria sinclairil. A series of alpha-mannosyl ceramide (alpha-ManCer) analogues was derived from 2-substituted 2-aminopropane-1,3-diols or 2-aminoethanols in place of sphingosine. The newly synthesized glycosides were evaluated for their effects on immune responses. In contrast to the immunosuppressive activity of the precursors, the alpha-ManCer analogues induced immunopromotive responses from invariant Valpha19-Jalpha26 transgenic mouse lymphocytes more effectively than the original alpha-ManCer. Collectively, it is strongly suggested that the 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols mimic sphingosine in the alpha-ManCer analogues so that they potentially acquire specific antigenicity toward Valpha19 NKT cell, a novel NKT cell subset.
2-取代的2-氨基丙烷-1,3-二醇或2-氨基乙醇是ISP-I（一种从中华被毛孢发酵液中分离出的抗生素）免疫抑制活性所需的最小结构。一系列α-甘露糖基神经酰胺（α-ManCer）类似物由2-取代的2-氨基丙烷-1,3-二醇或2-氨基乙醇取代鞘氨醇衍生而来。对新合成的糖苷的免疫反应作用进行了评估。与前体的免疫抑制活性相反，α-ManCer类似物比原始的α-ManCer更有效地诱导恒定链Vα19-Jα26转基因小鼠淋巴细胞产生免疫促进反应。总的来说，强烈表明2-取代的2-氨基丙烷-1,3-二醇和2-氨基乙醇在α-ManCer类似物中模拟鞘氨醇，因此它们可能获得针对Vα19 NKT细胞（一种新型NKT细胞亚群）的特异性抗原性。
