An approach for a synthesis of asparagine-linked sialylglycopeptides having intact and homogeneous complex-type undecadisialyloligosaccharides.
An approach for a synthesis of asparagine-linked sialylglycopeptides having intact and homogeneous complex-type undecadisialyloligosaccharides.
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DOI：
10.1002/chem.200600179
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发表时间：
2007-01
期刊：
影响因子：
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通讯作者：
Naoki Yamamoto;Ayumi Takayanagi;Ayako Yoshino;T. Sakakibara;Y. Kajihara
中科院分区：
文献类型：
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作者：
Naoki Yamamoto;Ayumi Takayanagi;Ayako Yoshino;T. Sakakibara;Y. Kajihara
本文介绍了天冬酰胺连接的唾液酸糖肽的合成。我们合成唾液酸糖肽的策略的典型特征是使用十一碳二唾液酸寡糖基Fmoc-天冬酰胺（Fmoc-Asn（CHO）-OH）1，除了NeuAc残基的苄基酯之外，其羟基上没有保护基团。我们的合成方法解决了在肽链延伸过程中由活化的氨基酸对糖羟基的酯化问题。当采用高浓度的Fmoc-氨基酸时，酯化显著发生，但当采用低浓度的反应物时，酯化几乎不发生。利用这些发现，我们研究了通过使用天然化学连接（NCL）合成具有两个复合型唾液酸寡糖的高分子唾液酸糖肽CTLA-4片段（113 - 150）13。结果，我们成功地合成了在N-末端具有半胱氨酸残基的唾液酸糖肽（CTLA-4：129 - 150片段）11和唾液酸糖肽硫酯（CTLA-4：113 - 128片段）12。最后，将合成的唾液酸糖肽应用于NCL反应。该反应成功地提供了所需的产物，CTLA-4（113 - 150）13，其包含具有优异纯度的成熟和纯的复合型唾液酸低聚糖。
This paper describes synthesis of asparagine-linked sialylglycopeptides. The typical feature of our strategy for the synthesis of a sialylglycopeptide is to employ undecadisialyloligosaccharyl Fmoc-asparagine (Fmoc-Asn(CHO)-OH) 1 without protecting groups on its hydroxyl groups except for the benzyl ester of the NeuAc residues. Our synthetic methodology solved the problem of esterification toward sugar hydroxyl groups by activated amino acids during the elongation of a peptide chain. When employing high concentrations of the Fmoc-amino acid, esterification markedly occurred, but the esterification scarcely occurred when employing low concentrations of reactants. Taking advantage of these findings, we examined the synthesis of a high molecular sialylglycopeptide, CTLA-4 fragment (113-150) 13 having two complex-type sialyloligosaccharides by use of native chemical ligation (NCL). As a result, we succeeded in the synthesis of a sialylglycopeptide having a cysteine residue at the N-terminus (CTLA-4: 129-150 fragment) 11 and a sialylglycopeptide-thioester (CTLA-4: 113-128 fragment) 12. Finally, the sialylglycopeptides synthesized were applied to NCL reactions. The reaction successfully afforded the desired product, CTLA-4 (113-150) 13 containing mature and pure complex-type sialyloligosaccharides in excellent purity.