Thiazolidine ring‐opening reaction is one of the key steps in protein chemical synthesis via sequential native chemical ligation strategy. We recently developed a novel thiazolidine ring‐opening reaction with 2,2′‐dipyridyl disulfide (DPDS). In order to investigate the applicability of this reaction to glycoprotein synthesis, we synthesized evasin‐3, a cysteine‐rich glycoprotein with chemokine‐binding ability originally found in tick saliva. The sequence of evasin‐3 was divided into three segments, and these segments were separately synthesized with the ordinary solid‐phase peptide synthesis method. After the first ligation of middle and C‐terminal segments, thiazolidine used as a protecting group of Cys residue at the N‐terminus of the middle segment was converted to Cys with DPDS. In this thiazolidine ring‐opening reaction, DPDS treatment did not affect the N‐linked glycan moiety. After the second ligation with the N‐terminal segment and the refolding reaction, evasin‐3 could be obtained in good yield. The synthetic evasin‐3 showed the binding ability specifically to CXCL chemokines. These results clearly indicate that this DPDS method is useful for glycoprotein synthesis.

中文翻译：

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2,2'-二吡啶基二硫化物介导的噻唑烷开环反应在糖蛋白合成中的应用：evasin-3的全化学合成

噻唑烷开环反应是通过顺序天然化学连接策略进行蛋白质化学合成的关键步骤之一。我们最近开发了一种新的噻唑烷与 2,2'-二吡啶基二硫化物 (DPDS) 的开环反应。为了研究该反应对糖蛋白合成的适用性，我们合成了 evasin-3，这是一种富含半胱氨酸的糖蛋白，具有最初在蜱唾液中发现的趋化因子结合能力。evasin-3的序列分为三个片段，这些片段分别用普通固相肽合成方法合成。在第一次连接中间和 C 端片段后，用作中间片段 N 端 Cys 残基保护基的噻唑烷用 DPDS 转化为 Cys。在这个噻唑烷开环反应中，N-连接的聚糖部分。在与 N 端片段的第二次连接和重折叠反应后，可以以良好的收率获得 evasin-3。合成的 evasin-3 显示出对 CXCL 趋化因子的特异性结合能力。这些结果清楚地表明这种 DPDS 方法可用于糖蛋白合成。