权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Synthesis of Dendrimer-Type AIDS Vaccine having Cyclic Peptide Antigen

具有环肽抗原的树枝状聚合物型艾滋病疫苗的合成

基本信息

批准号：
14550840
负责人：
URYU Toshiyuki
金额：
$ 1.92万
依托单位：
Teikyo University of Science and Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

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.

对球形树状大分子艾滋病疫苗的合成进行了研究。以1，4-二氨基丁烷为核心化合物，合成了球形聚(赖氨酸)树枝状大分子第三代(G3)。β-丙氨酸与树枝状大分子的末端氨基结合，得到伪聚赖氨酸树枝状大分子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-聚赖氨酸树枝状大分子与天然蛋白质一样呈单分散的分子量分布。低聚糖-β-丙氨酸-聚赖氨酸树状大分子有32个寡糖单元，其中两个连接在β-丙氨酸-聚赖氨酸树枝状大分子的16个氨基末端，其相对分子质量约为13453，接近理论分子量。另一方面，当用聚鸟氨酸树枝状大分子代替多赖氨酸树状大分子时，球状低聚糖-β-丙氨酸-聚鸟氨酸树枝状大分子的相对分子质量为11900~13200，取代低聚糖的数量为28~32个。此外，当制备半球形的Pro-聚(赖氨酸)树枝状大分子并与麦芽糖反应时，得到了单分散的分子量约为4400的麦芽糖-Pro-聚(赖氨酸)树状大分子。此外，还合成了琥珀酰麦芽糖-Pro-聚赖氨酸树枝状大分子，并与艾滋病病毒24个氨基酸残基组成的线性多肽抗原反应，得到了树状大分子型艾滋病疫苗候选疫苗，其中1-2个抗原肽通过氨基连接到琥珀酸基上。