Synthesis of Dendrimer-Type AIDS Vaccine having Cyclic Peptide Antigen

研究了球形树状高分子艾滋病疫苗的合成。以1，4-丁二胺为核心化合物，合成了第三代球形聚赖氨酸树枝状大分子（G3）。将β-丙氨酸结合到树枝状聚合物的末端氨基，得到假聚（赖氨酸）树枝状聚合物G4。将β-丙氨酸-聚赖氨酸树状大分子与乳糖、麦芽糖、纤维二糖等寡糖进行还原胺化反应，得到的寡糖-β-丙氨酸-聚赖氨酸树状大分子具有与天然蛋白质相似的单分散分子量分布。寡糖-β-丙氨酸-聚（赖氨酸）树枝状聚合物具有32个寡糖单元，其中两个分别连接到β-丙氨酸-聚（赖氨酸）树枝状聚合物的末端16个氨基，显示出接近理论分子量的约13453的分子量。当用聚鸟氨酸树枝状大分子代替聚赖氨酸树枝状大分子时，球状寡糖-β-丙氨酸-聚鸟氨酸树枝状大分子的分子量为11900 ~ 13200，取代寡糖数为28 ~ 32。此外，当制备半球形脯氨酸-聚（赖氨酸）树枝状聚合物并与麦芽糖反应时，获得具有约4400的单分散分子量的麦芽糖-脯氨酸-聚（赖氨酸）树枝状聚合物。合成了琥珀酰-麦芽糖-脯氨酸-多聚赖氨酸树枝状大分子，并将其与由24个氨基酸残基组成的艾滋病病毒线性多肽抗原反应，得到了一种树枝状大分子型艾滋病疫苗候选物，其中1 ~ 2个抗原肽通过酰胺键与琥珀酰基团结合。

Synthesis of spherical dendrimer-type AIDS vaccine was investigated. Spherical polyl(ysine) dendrimer generation three (G3), which can be regarded as a didendron, was synthesized starting from 1,4-diaminobutane as a core compound. β-Alanine was bound to the terminal amino group of the dendrimer to afford pseudo poly(lysine) dendrimer G4. When β-alanine-poly(lysine) dendrimer was reacted by reductive amination with such oligosaccharides as lactose, maltose, and cellobiose, the resulting oligosaccharide-β-alanine-poly(lysine) dendrimer showed monodispersed molecular weight distribution like natural proteins. The oligosaccharide-β-alanine-poly(lysine) dendrimer had 32 oligosaccharide units the two each of which were connected to the terminal 16 amino groups of the β-alanine-poly(lysine) dendrimer, showing a molecular weight of approximately 13453 close to the theoretical molecular weight. On the other hand, when poly(ornithine) dendrmer was used instead of poly(lysine) dendrimer, sperical oligosaccharide-β-alanine-poly(rnithine) dendrimers showed the molecular weight of 11900 to 13200 and the number of substituted oligosaccharides of 28 to 32. Furthermore, when hemispherical proline-poly(lysine) dendrimer was prepared and reacted with maltose, maltose-proline-poly(lysine) dendrimer having a monodispersed molecular weight of approximately 4400 was obtained. Furthermore, succinyl-maltose-proline-poly(lysine) dendrimer was synthesized and reacted with linear polypeptide antigen from AIDS virus consisting of 24 amino residues to give a dendrimer-type AIDS vaccine candidate in which one to two antigen peptides were bound to the succinyl group through amido linkage.