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Synthesis of Dendrimer-Type AIDS Vaccine Having High Antibody Productivity

高抗体生产力树枝状聚合物型艾滋病疫苗的合成

基本信息

批准号：
12650873
负责人：
URYU Toshiyuki
金额：
$ 2.3万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

分子设计和合成了具有高抗HIV（人类免疫缺陷病毒）活性的可能性的树枝状聚合物型AIDS（获得性免疫缺陷综合征）疫苗。预期携带高抗原性HIV肽序列的中等分子量树枝状聚合物型疫苗可产生大量抗体。赖氨酸树枝状聚合物第三代（G3）和第四代（G4）以及鸟氨酸树枝状聚合物第三代用于核心树枝状聚合物。开发了在温和条件下将HIV gp 120中包含的肽序列与树枝状聚合物结合的两种方法。在第一种方法中，赖氨酸树枝状聚合物G3中的8个氨基与乳糖、麦芽糖和麦芽三糖通过使用BH 3吡啶催化剂的还原胺化反应，以产生至多16个寡糖结合的树枝状聚合物。在接下来的树枝状聚合物延伸中，寡糖中的伯6-OH基团与二元酸如己二酸和辛二酸反应，得到二元酸-寡糖-赖氨酸树枝状聚合物三层树枝状聚合物。还制备了一种四层结构的树枝状大分子。在第二种方法中，合成纤维二糖-赖氨酸树状聚合物，其中纤维二糖部分的还原末端指向树状聚合物外。在还原末端，尝试通过还原胺化结合HIV环肽以形成AIDS疫苗。通过核磁共振和飞行时间质谱对产物的结构和分子量进行了表征，得到了一种艾滋病疫苗的模型化合物。通过NMR检测多肽和多糖之间的分子间相互作用，以分析生物活性大分子如疫苗的作用机制。