Synthesis of Dendrimer-Type AIDS Vaccine Having High Antibody Productivity

摘要设计并合成了一种可能具有高抗hiv活性的树突型艾滋病疫苗。预计携带高抗原性HIV肽序列的中等分子量树突状疫苗可产生大量抗体。核心树状大分子采用赖氨酸树状大分子第三代（G3）和第四代（G4），鸟氨酸树状大分子第三代。开发了两种方法，在温和条件下将HIV gp120中包含的肽序列结合到树突上。在第一种方法中，赖氨酸树状大分子G3中的8个氨基在BH3吡啶催化剂下与乳糖、麦芽糖和麦芽糖三糖进行还原性胺化反应，生成最多16个寡糖结合树状大分子。在接下来的枝状大分子延伸中，低聚糖中的伯6-OH与己二酸和亚亚酸等二酸反应，得到二酸-低聚糖-赖氨酸枝状大分子三层。还制备了一种四层树状大分子。第二种方法是合成纤维素二糖-赖氨酸树状大分子，其中纤维素二糖部分的还原端指向树状大分子外。在还原端，HIV环肽试图通过还原胺化结合形成艾滋病疫苗。通过NMR和TOF-MS测定了产物的结构和分子量。获得了一种艾滋病疫苗模型化合物。利用核磁共振技术检测多肽与多糖的分子间相互作用，分析疫苗等生物活性大分子的作用机制。

A dendrimer-type AIDS (acquired immunodeficiency syndrome) vaccine having a possibility of high anti-HIV (human immunodeficiency virus) activity was molecularly designed and synthesized. It is expected that a medium molecular weight dendrimer-type vaccine carrying highly antigenic HIV peptide sequence can produce a large quantity of antibodies. Lysine dendrimer third (G3) and fourth (G4) generations, and ornithine dendrimer third generation were used for core dendrimers. Two methods by which a peptide sequnece included in HIV gp120 was bound to the dendrimer under mild conditions were developed. In the first method, eight amino groups in lysine dendrimer G3 were reacted with lactose, maltose, and maltotriose by reductive amination using BH3 pyridine catalyst to produce at most 16 oligosaccharides-bound dendrimers. In the next dendrimer elongation, primary 6-OH groups in the oligosaccharide were reacted with such dibasic acids as adipic acid and suberic acid to give dibasic acid-oligosaccharide-lysine dendrimer three-layered dendrimers. A four-layered dendrimer was also preprared. In the second method, cellobiose-lysine dendrimer was synthesized in which reducing end of the cellobiose moiety was directed outward the dendrimer. To the reducing end, a HIV cyclic peptide was tried to bind by reductive amination to form AIDS vaccine. Structure and molecular weight of the products were determined by NMR and TOF-MS. A model compound for AIDS vaccine was obtained. Intermolecular interactions between polypeptide and polysaccharide were detected by NMR in order to analyze an action mechanism of biologically active macromolecules such as vaccine.