Synthesis of Dendrimer-Type AIDS Vaccine having Cyclic Peptide Antigen

研究了球形树突型艾滋病疫苗的合成。以1,4-二氨基丁烷为核心化合物，合成了球形聚赖氨酸树状大分子第三代（G3），可视为双枝状。β-丙氨酸与树状大分子末端氨基结合形成伪聚赖氨酸树状大分子G4。当β-丙氨酸-聚赖氨酸树状大分子与乳糖、麦芽糖、纤维素二糖等低聚糖进行还原胺化反应时，得到的低聚糖-β-丙氨酸-聚赖氨酸树状大分子表现出与天然蛋白质一样的单分散分子量分布。低聚糖-β-丙氨酸-聚（赖氨酸）树状大分子有32个低聚糖单元，其中两个单元分别连接在β-丙氨酸-聚（赖氨酸）树状大分子的末端16个氨基上，其分子量约为13453，接近理论分子量。另一方面，当用聚鸟氨酸树状大分子代替聚赖氨酸树状大分子时，精子寡糖-β-丙氨酸-聚鸟氨酸树状大分子的分子量为11900 ~ 13200，取代的寡糖数为28 ~ 32。此外，当制备半球形脯氨酸-聚赖氨酸树状大分子并与麦芽糖反应时，得到单分散分子量约为4400的麦芽糖-脯氨酸-聚赖氨酸树状大分子。此外，我们还合成了琥珀酰-麦芽糖-脯氨酸-聚赖氨酸树突状分子，并与由24个氨基残基组成的艾滋病病毒线状多肽抗原反应，得到了一到两个抗原肽通过氨基连锁结合到琥珀酰基上的树突状艾滋病候选疫苗。

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.