PROPERTIES OF A SYNTHETIC ANTIGEN RELATED TO HUMAN BLOOD-GROUP LEWIS-A
PROPERTIES OF A SYNTHETIC ANTIGEN RELATED TO HUMAN BLOOD-GROUP LEWIS-A
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DOI：
10.1021/ja00847a035
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发表时间：
1975-01-01
影响因子：
15
通讯作者：
BAKER, DA
中科院分区：
文献类型：
--
作者：
LEMIEUX, RU;BUNDLE, DR;BAKER, DA
(2-乙酰氨基-2-脱氧-D-吡喃葡萄糖的3-糖苷、2-乙酰氨基-2-脱氧-4-0-(α-L-吡喃岩藻糖基)-D-吡喃葡萄糖、2-乙酰氨基-2-脱氧-3-<9-(对-D-吡喃半乳糖基)-D-吡喃葡萄糖的3-糖苷，和使用8-乙氧基羰基-或8-甲氧基羰基-1-辛醇合成2-乙酰氨基-2-脱氧-4-0-(αL-吡喃岩藻糖基)-3-0-((3-D-吡喃半乳糖基)-D-吡喃葡萄糖。通过将这些酯附着到牛血清白蛋白中的游离氨基来制备半合成抗原。用三糖产生的抗体具有人类血型 Lewis a (Lea) 决定簇末端三糖单元的抗原沉淀了天然血型 Lea 物质并凝集了 Lea 红细胞。其他免疫化学交叉反应以及抑制实验也有报道。使用所谓的肟基氯化物 3'4 和卤化物离子 5-7 催化糖苷化反应合成寡糖结构所取得的成功预示着能够合成大部分的寡糖结构。多糖、糖蛋白和糖脂抗原的寡糖抗原决定簇迄今为止在这方面最值得注意的成就是 3-0-(2-乙酰氨基-2-脱氧-α-D-吡喃半乳糖基)-D-吡喃半乳糖（人血型 A 决定簇的末端二糖单位）的合成，8 2-0-(α-L-吡喃岩藻糖基)-3-0-(α-D-吡喃半乳糖基)-D-半乳糖（人血型 B 决定簇的末端三糖单元）、7 2-0-(αL-吡喃岩藻糖基)-D-半乳糖（人血型 O (H) 决定簇的末端二糖单元）、7'9 和2-乙酰氨基-2-脱氧-4-0-(α-L-吡喃岩藻糖基)-3-0-(/3-D-吡喃半乳糖基)-D-葡萄糖（人类 Lea 血型的末端三糖单元）6 首次建立了这些还原寡糖的合成方法，主要用于将合成产物与通过血型糖蛋白水解获得的产物进行比较。然而，还原性寡糖的合成本身价值有限，这种合成在本实验室已基本停止，现在的注意力集中在糖苷形式的寡糖的合成上，糖苷可以作为寡糖与高分子量物质连接的桥梁，因此，与蛋白质或其他高聚物的共价连接将提供用于研究碳水化合物抗原的免疫化学和免疫学的抗原。这种基于化学合成的发展的免疫化学方面被认为特别令人兴奋，因为这将允许以这样的方式研究化学修饰的抗原，从而可能对与抗体活性位点的结合机制提供重要的见解。
The (3-glycosides of 2-acetamido-2-deoxy-D-glucopyranose, 2-acetamido-2-deoxy-4-0-(aL-fucopyranosyl)-D-glu-copyranose, 2-acetamido-2-deoxy-3-< 9-(/?-D-galactopyranosyl)-D-glucopyranose, and 2-acetamido-2-deoxy-4-0-(aL-fucopyranosyl)-3-0-((3-D-galactopyranosyl)-D-glucopyranose were synthesized, using either 8-ethoxycarbonyl-or 8-methoxycar-bonyl-l-octanol. Semisyntheticantigens were prepared from theseest'ers by attachment to the free amino groups in bovine serum albumin. The antibodies raised with the trisaccharide antigen which possesses the terminal trisaccharide unit of the human blood-group Lewis a (Lea) determinant precipitated natural blood-group Lea substance and agglutinated Lea red blood cells. Other immunochemical cross-reactions as well as inhibition experiments are reported.The success achieved in the synthesis of oligosaccharide structures using the so-called oximinochloride3'4 and halide ion5-7 catalyzed glycosidation reactions augurs well for a capability to synthesize substantial portions of the oligosac-charide antigenic determinants of polysaccharide, glycoprotein, and glycolipid antigens. The most noteworthy achievements to date in this regard were the syntheses of 3-0-(2-acetamido-2-deoxy-aD-galactopyranosyl)-D-galactopyran-ose (the terminal disaccharide unit of the human bloodgroup A determinant), 8 2-0-(aL-fucopyranosyl)-3-0-(a-D-gaIactopyranosyI)-D-galactose (the terminal trisacchar-ide unit of the human blood-group B determinant), 7 2-0-(aL-fucopyranosyl)-D-galactose (the terminal disaccharide unit of the human blood-group O (H) determinant), 7'9 and 2-acetamido-2-deoxy-4-0-(aL-fucopyranosyl)-3-0-(/3-D-galactopyranosyl)-D-glucose (the terminal trisaccharide unit of the human blood-group Lea). 6 Methodology was es-tablished in the first instance for the synthesis of these re-ducing oligosaccharides primarily forthe comparison of the synthetic products with those obtained by hydrolysis of the blood-group glycoproteins. However, the synthesis of reduc-ing oligosaccharides per se is of limited value, and such syn-theses have been largely discontinued in this laboratory. In-stead, attention is now focused on the synthesis of the oligo-saccharides in the form of glycosides that possess an agly-con which can serve as a bridge for the attachment of the oligosaccharide to high molecular weight substances. Thus, covalent attachment to proteins or other high polymers would provide antigens with which to study the immunochemistry and immunology of carbohydrate antigens. The immunochemical aspects of such developments based in chemical synthesis are considered particularly exciting since these would allow the study of chemically modified antigens in such a way as perhaps to shed important insight on the mechanism of the binding with the active sites of the antibody.