Glycoprotein Semisynthesis by Chemical Insertion of Glycosyl Asparagine Using a Bifunctional Thioacid-Mediated Strategy
Glycoprotein Semisynthesis by Chemical Insertion of Glycosyl Asparagine Using a Bifunctional Thioacid-Mediated Strategy
复制标题
使用双功能硫代酸介导的策略通过化学插入糖基天冬酰胺来半合成糖蛋白
DOI：
10.1021/jacs.1c02601
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发表时间：
2021
影响因子：
15
通讯作者：
and Yasuhiro Kajihara
中科院分区：
文献类型：
--
作者：
Kota Nomura;Yuta Maki;Ryo Okamoto;Ayano Satoh;and Yasuhiro Kajihara
糖基化是分泌蛋白和细胞表面蛋白的主要修饰，所得聚糖在结构上表现出相当大的异质性。为了了解每种糖型产生的生物过程，均质糖蛋白的制备对于广泛的生物实验至关重要。为了建立更稳健、更快速的合成均质糖蛋白的合成路线，我们研究了基于氨基酸硫代酸的几个关键反应。我们发现二酰基二硫键与糖基天冬酰胺硫代酸和肽硫代酸形成二酰基二硫偶联（DDC）产生糖肽。这种高效的偶联反应使我们能够开发出一种新的糖蛋白合成方法，例如双功能硫代酸介导的策略，该策略可以将两个肽与糖基天冬酰胺硫代酸的N端和C端偶联。以前的糖蛋白合成方法在早期需要有价值的糖基天冬酰胺以及随后的多种糖蛋白合成路线，而开发的概念可以在几个步骤内从肽和糖基天冬酰胺硫代酸生成糖蛋白。在此，我们报告了氨基硫代酸 DDC 的表征以及糖基天冬酰胺硫代酸用于稳健糖蛋白半合成的有效能力。
Glycosylation is a major modification of secreted and cell surface proteins, and the resultant glycans show considerable heterogeneity in their structures. To understand the biological processes arising from each glycoform, the preparation of homogeneous glycoproteins is essential for extensive biological experiments. To establish a more robust and rapid synthetic route for the synthesis of homogeneous glycoproteins, we studied several key reactions based on amino thioacids. We found that diacyl disulfide coupling (DDC) formed with glycosyl asparagine thioacid and peptide thioacid yielded glycopeptides. This efficient coupling reaction enabled us to develop a new glycoprotein synthesis method, such as the bifunctional thioacid-mediated strategy, which can couple two peptides with the N- and C-termini of glycosyl asparagine thioacid. Previous glycoprotein synthesis methods required valuable glycosyl asparagine in the early stage and subsequent multiple glycoprotein synthesis routes, whereas the developed concept can generate glycoproteins within a few steps from peptide and glycosyl asparagine thioacid. Herein, we report the characterization of the DDC of amino thioacids and the efficient ability of glycosyl asparagine thioacid to be used for robust glycoprotein semisynthesis.