Application of 2,2′‐dipyridyl disulfide‐mediated thiazolidine ring‐opening reaction to glycoprotein synthesis: Total chemical synthesis of evasin‐3
Application of 2,2′‐dipyridyl disulfide‐mediated thiazolidine ring‐opening reaction to glycoprotein synthesis: Total chemical synthesis of evasin‐3
复制标题
2,2-二吡啶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
DOI：
10.1002/psc.3290
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发表时间：
2020
影响因子：
2.1
通讯作者：
Nagata Koji
中科院分区：
文献类型：
--
作者：
Katayama Hidekazu;Nagata Koji
噻唑烷开环反应是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开环反应与2,2 ' -二硫化二吡啶（DPDS）。为了研究该反应在糖蛋白合成中的适用性，我们合成了evasin‐3，这是一种富含半胱氨酸的糖蛋白，具有趋化因子结合能力，最初在蜱虫唾液中发现。evasin‐3的序列被分成三个片段，这些片段分别用普通固相肽合成法合成。在第一次连接中间和C端片段后，在中间片段N端作为Cys残基保护基团的噻唑烷用DPDS转化为Cys。在这个噻唑烷开环反应中，DPDS处理不影响theN - linked glycan部分。通过与N端段的第二次连接和再折叠反应，可以获得高收率的evasin - 3。合成的evasin‐3显示出特异性结合CXCL趋化因子的能力。这些结果清楚地表明DPDS方法在糖蛋白合成中是有用的。
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 theN‐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.