Access to lipopeptide-based vaccines for immunological studies remains a significant challenge owing to the amphipathic nature of the molecules, which makes them difficult to synthesize and purify to homogeneity. Here, we describe the application of a new peptide ligation technology, the diselenide-selenoester ligation (DSL), to access self-adjuvanting glycolipopeptide vaccines. We show that rapid ligation of glyco- and lipopeptides is possible via DSL in mixed organic solvent-aqueous buffer and, when coupled with deselenization chemistry, affords rapid and efficient access to a vaccine candidate possessing a MUC1 glycopeptide epitope and the lipopeptide adjuvant Pam₂Cys. This construct was shown to elicit MUC1-specific antibody and cytotoxic T lymphocyte responses in the absence of any other injected lipids or adjuvants. The inclusion of the helper T cell epitope PADRE both boosted the antibody response and resulted in elevated cytokine production.

中文翻译：

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通过二硒化物-硒酸酯连接-二硒化合成自佐剂MUC1疫苗。

由于分子的两亲性质，获得基于脂肽的疫苗进行免疫学研究仍然是一个重大挑战，这使得它们难以合成和纯化至均一。在这里，我们描述了一种新的肽连接技术，二硒代硒酸酯连接（DSL）的应用，以访问自我辅助的糖脂肽疫苗。我们显示糖和脂肽的快速连接是可能的，可以通过DSL在混合的有机溶剂-水缓冲液中进行，并结合去硒化化学，可以快速有效地获得拥有MUC1糖肽表位和脂肽佐剂Pam _2的候选疫苗半胱氨酸 在没有任何其他注射脂质或佐剂的情况下，该构建体可引发MUC1特异性抗体和细胞毒性T淋巴细胞应答。包含辅助T细胞表位PADRE既增强了抗体应答，又导致细胞因子产生增加。