Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide

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• 作者：Yasuhiro Kajihara ; Akiko Yoshihara ; Kiriko Hirano and Naoki Yamamoto
• 关键词：Glycopeptide ; Complex-type oligosaccharide ; Thioester ; Solid-phase peptide synthesis ; Sialyl-oligosaccharyl-peptide
• 刊名：Carbohydrate Research
• 出版年：2006
• 出版时间：24 July 2006
• 年：2006
• 卷：341
• 期：10
• 页码：1333-1340
• 全文大小：358 K

文摘

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 °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.