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首页> 外文期刊>Chemistry: A European journal >Synthesis of a Structurally Defined Antigen - Immunostimulant Cmbination for Use in Cancer Vaccines
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Synthesis of a Structurally Defined Antigen - Immunostimulant Cmbination for Use in Cancer Vaccines

机译：用于癌症疫苗的结构确定的抗原-免疫刺激结合的合成

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Ganglioside GM_2 expressed on the cell surfae of human cancers is a promising target for immunotherapy because GM_2 antibodies are cytotoxic in vitro and GM_2 antibody formation can be induced upon vaccination in cancer patients. We recently reported on the efficient chemcial synthesis of GM_2; clinical trials with these synthetic GM_2 conjugated to a purified carrier protein (KLH) are currently under way. In our efforts to generate a totally synthetic GM_2 ancer vaccine, we have now synthesized GM_2 neoglycolpid 1, which consiists of the GM_2-tetrasaccharide epitope that is linked through a spacr tot he B-cell stimulatory glycolipid 4. Target compound 1 was constructred from the GM_2 tetrasaccharide donor 2, the 9-hydroxynonanoate 3 spacer, and the 6-amino-6-deoxy derivative (5) of compound 4. Building block 5 was obtained from Z-protected 6-azido-6-deoxy-N-leucyl-glucosamine derivative 12, which was available from glucosamine by two different approaches; the route with the Z-protected derivative of 4 (10) as intermediate gave the best yields. The neoglycolipid 1 reacted with a number of different GM_2-reactive antibodies. Vaccination of rabbits with 1 resulted in induction of antibodies against GM_2, thus confirming the viability of this novel concept for the construction of a totally synthetic vac-cine.
机译：在人类癌症细胞表面上表达的神经节苷脂GM_2是免疫治疗的有希望的靶标，因为GM_2抗体​​在体外具有细胞毒性，并且在癌症患者中接种疫苗后可以诱导GM_2抗体​​形成。我们最近报道了GM_2的有效化学合成。这些合成的GM_2与纯化的载体蛋白（KLH）结合的临床试验目前正在进行中。在我们努力产生完全合成的GM_2癌疫苗的过程中，我们现在合成了GM_2新糖脂1，它由GM_2-四糖表位组成，该表位通过B细胞刺激糖脂4相连。化合物4的GM_2四糖供体2、9-羟基壬酸3间隔基和6-氨基-6-脱氧衍生物（5）。结构单元5由Z-保护的6-叠氮基6-脱氧-N-亮氨酰基-获得。葡糖胺衍生物12，可以通过两种不同的方法从葡糖胺获得;以4（10）的Z保护衍生物为中间体的路线收率最高。新糖脂1与许多不同的GM_2反应性抗体反应。用1接种兔子会诱导针对GM_2的抗体的诱导，从而证实了这种新颖概念对于构建完全合成的疫苗的可行性。

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