Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide
Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide
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DOI：
10.1016/j.carres.2006.04.037
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发表时间：
2006-07-24
影响因子：
3.1
通讯作者：
Yamamoto, Naoki
中科院分区：
文献类型：
--
作者：
Kajihara, Yasuhiro;Yoshihara, Akiko;Yamamoto, Naoki
获得具有C-末端硫酯官能团的糖肽对于通过使用天然化学连接合成大的糖肽和糖蛋白是必不可少的。为此，我们开发了一种简洁的方法，用于合成具有完整的复合型二支化二唾液酸寡糖的糖肽硫酯。该合成采用苄硫醇和糖肽C-末端的游离羧酸之间的偶联反应，其中肽侧链被保护。通过Fmoc策略在HMPB-PEGA树脂上构建糖肽后，用乙酸/三氟乙醇处理后释放受保护的糖肽，然后在-20 ° C下在DMF中将C-末端羧酸与苄硫醇偶联。对于这种偶联，发现PyBOP/DIPEA对于硫酯的形成是最好的，同时避免外消旋化。最后，用95%TFA以良好的产率除去保护基，从而得到具有完整和均匀的复合型二唾液酸寡糖的糖肽硫酯。(c)2006爱思唯尔有限公司版权所有。
Access to glycopeptides with C-terminal thioester functionality is essential for the synthesis of large glycopeptides and glycoproteins through the use of native chemical ligation. Toward that end, we have developed a concise method for the synthesis of a glycopeptide thioester having an intact complex-type dibranched disialyl-oligosaccharide. The synthesis employed a coupling reaction between benzylthiol and a free carboxylic acid at the C-terminus of a glycopeptide in which the peptide side chains are protected. After construction of glycopeptide on the HMPB-PEGA resin through the Fmoc-strategy, the protected glycopeptide was released upon treatment with acetic acid/trifluoroethanol and then the C-terminal carboxylic acid was coupled with benzylthiol at -20 degrees C in DMF. For this coupling, PyBOP/DIPEA was found to be the best for the formation of the thioester, while avoiding racemization. Finally, the protecting groups were removed in good yield with 95% TFA, thus affording a glycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide. (c) 2006 Elsevier Ltd. All rights reserved.