Chemical synthesis of alpha-L-fucopyranosylceramide and its analogues and preparation of antibodies directed to this glycolipid.
Chemical synthesis of alpha-L-fucopyranosylceramide and its analogues and preparation of antibodies directed to this glycolipid.
复制标题
α-L-吡喃岩藻糖神经酰胺及其类似物的化学合成以及针对该糖脂的抗体的制备。
作者：
T. Yoshino;K. Watanabe;S. Hakomori
一种新型糖脂，α-L-吡喃岩藻糖神经酰胺，先前从转移性人腺癌中分离和表征[Watanabe, K., Matsubara, T., & Hakomori, S. (1976) J. Biol.化学。 251、2385-2387]。为了进一步研究这种糖脂及其特异性抗体的病理生物学意义，通过 2,3,4-三-O-苄基-α-L-吡喃岩藻糖基溴和神经酰胺的 Königs-Knorr 型缩合化学合成抗原糖脂 α-L-吡喃岩藻糖神经酰胺，然后通过催化氢化去除苄基。还合成了α-L-吡喃岩藻糖基-N-棕榈酰乙醇胺和2,3,4-三-O-苄基-α-L-吡喃岩藻糖基鞘氨醇。针对脂质体中包含的合成α-L-吡喃岩藻糖基神经酰胺制备的抗体与从人腺癌分离的合成和天然α-L-吡喃岩藻糖基神经酰胺反应良好，但补体依赖性脂质体裂解动力学和合成岩藻糖神经酰胺的补体固定模式与天然岩藻糖神经酰胺显着不同。天然岩藻糖神经酰胺的免疫原性比合成岩藻糖神经酰胺弱得多。合成和天然岩藻糖神经酰胺在脂质体裂解、补体固定和免疫原性方面的显着差异一定是由于神经酰胺结构的差异所致。结果表明，糖脂的抗原性和免疫原性的强度可能很大程度上取决于神经酰胺结构，而特异性仅由糖部分决定。抗-α-L-岩藻糖神经酰胺抗体表现出与半乳糖神经酰胺、神经酰胺和单独的脂质体的交叉反应性，该交叉反应性通过半乳糖神经酰胺脂质体的吸收而消除。
A novel glycolipid, alpha-L-fucopyranosylceramide, was previously isolated and characterized from metastatic human adenocarcinoma [Watanabe, K., Matsubara, T., & Hakomori, S. (1976) J. Biol. Chem. 251, 2385-2387]. For further investigation of the pathobiological significance of this glycolipid with its specific antibodies, the antigen glycolipid alpha-L-fucopyranosylceramide was chemically synthesized by Königs-Knorr-type condensation of 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide and a ceramide, followed by removal of benzyl groups by catalytic hydrogenation. alpha-L-Fucopyranosyl-N-palmitoylethanolamine and 2,3,4-tri-O-benzyl-alpha-L-fucopyranosylsphingosine were also synthesized. The antibodies prepared against a synthetic alpha-L-fucopyranosyl-ceramide included in liposome reacted very well with the synthetic as well as the natural alpha-L-fucopyranosylceramide isolated from human adenocarcinoma, but the kinetics of the complement-dependent liposome lysis and the complement fixation pattern with the synthetic fucosylceramide were significantly different from those with the natural fucosylceramide. The natural fucosylceramide showed a much weaker immunogenicity than the synthetic fucosylceramide. The remarkable difference in liposome lysis, complement fixation, and immunogenicity between the synthetic and the natural fucosylceramide must be due to the difference in ceramide structures. The results indicate that the strength of antigenicity and immunogenicity of glycolipids may greatly depend on ceramide structure, whereas the specificity is solely determined by the sugar moiety. The anti-alpha-L-fucosylceramide antibodies display cross-reactivity with galactosylceramide, ceramide, and liposome alone that was eliminated by absorption with galactosylceramide liposomes.
肿瘤相关神经节-N-三糖神经酰胺。
DOI：
--
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Urdal,DL;Hakomori,S
通讯作者：
Hakomori,S