Matsumoto Kenjiro, Takenouchi Mika, Ohta Keisuke, Ohta Yumiko, Imura Tomohiro, Oshige Masahiko, Yamamoto Yoshiteru, Sahara Hiroeki, Sakai Hideki, Abe Masahiko, Sugawara Fumio, Sato Noriyuki, Sakaguchi Kengo
Department of Applied Biological Science, Science University of Tokyo, 2641 Yamazaki, Noda-shi, Chiba-ken 278-8510, Japan.
Biochem Pharmacol. 2004 Dec 15;68(12):2379-86. doi: 10.1016/j.bcp.2004.08.020.
The immunosuppressive effects of synthetic sulfo-glycolipids in the class of sulfoquinovosyl-diacylglycerols (SQDG), including stereoisomers, were interesting in development of a promising clinical drug. Especially, 1,2-di-O-stearoyl-3-O-(6-deoxy-6-sulfo-beta-D-glucopyranosyl)-sn-glycerol (beta-SQDG-C18) was thought to be a valuable candidate because of the preliminary observations of its high inhibitory activities in spite of low toxicities. The problem of using this material is to find an applicable way avoiding its low solubility in water. The vesicle formation of beta-SQDG-C18 is advantageous to i.v. administration in its chemico-structural character. With preparation in water, beta-SQDG-C18 was hard to form vesicles, because its hydrophilicity was strong. We examined the suitable parameter of the vesicle forming condition. It was possible to take a balance between the hydrophilicity and the hydrophobicity of the beta-SQDG-C18 molecule to be optimized to form vesicles in 150 mM PBS. In addition, we demonstrated the strong immunosuppressive activity of beta-SQDG-C18 vesicles. This is the first report of the preparation method of beta-SQDG-C18 vesicles, which should facilitate in vitro and in vivo application.
包括立体异构体在内的磺基喹喔啉基二酰基甘油（SQDG）类合成磺基糖脂的免疫抑制作用，在开发一种有前景的临床药物方面具有重要意义。特别是，1,2-二-O-硬脂酰基-3-O-(6-脱氧-6-磺基-β-D-吡喃葡萄糖基)-sn-甘油（β-SQDG-C18）因其尽管毒性低但初步观察到具有高抑制活性，被认为是一个有价值的候选物。使用这种材料的问题在于找到一种适用的方法来避免其在水中的低溶解度。β-SQDG-C18的囊泡形成在其化学结构特征上有利于静脉内给药。在水中制备时，β-SQDG-C18很难形成囊泡，因为其亲水性很强。我们研究了囊泡形成条件的合适参数。在150 mM PBS中，可以在β-SQDG-C18分子的亲水性和疏水性之间取得平衡以优化形成囊泡。此外，我们证明了β-SQDG-C18囊泡具有很强的免疫抑制活性。这是关于β-SQDG-C18囊泡制备方法的首次报道，这将有助于其在体外和体内的应用。
