Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies
Chemical synthesis of a glycoprotein having an intact human complex-type sialyloligosaccharide under the Boc and Fmoc synthetic strategies
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DOI：
10.1021/ja072543f
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发表时间：
2008-01-16
影响因子：
15
通讯作者：
Kajihara, Yasuhiro
中科院分区：
文献类型：
--
作者：
Yamamoto, Naoki;Tanabe, Yasutaka;Kajihara, Yasuhiro
复杂糖蛋白的化学合成是蛋白质化学中持续存在的挑战：我们研究了单核细胞趋化蛋白 3 (MCP-3) 的单一糖型的合成，MCP-3 是一种 CC 趋化因子，由 76 个氨基酸和一个 N-糖基化位点组成。使用未受保护的肽和糖肽采用三段天然化学连接策略。重要的是，合成需要开发唾液酸糖肽-(α)硫酯的生成方法。对于唾液酸糖肽-(α)硫酯片段，我们使用 Fmoc-SPPS 和 Boc-SPPS 检查并成功实施了方法。为了避免使用氟化氢，Boc 方法利用了最少的侧链保护和树脂结合肽的直接硫解。利用这些策略，我们成功合成了具有完整且均质的复合型唾液酸寡糖的糖蛋白。
The chemical synthesis of complex glycoproteins is an ongoing challenge,in protein chemistry: We have examined the synthesis of a single glycoform of monocyte chemotactic protein-3 (MCP-3), a CC-chemokine that consists of 76 amino acids and one N-glycosylation site. A three-segment native chemical ligation strategy was employed using unprotected peptides and glycopeptide. Importantly, the synthesis required the development of methods for the generation of sialylglycopeptide-(alpha)thioesters. For the sialylglycopeptide-(alpha)thioester segment, we examined and successfully implemented approaches using Fmoc-SPPS and Boc-SPPS. To avoid use of hydrogen fluoride, the Boc approach utilized minimal side chain protection and direct thiolysis of the resin bound peptide. Using these strategies, we successfully synthesized a glycoprotein having an intact and homogeneous complex-type sialyloligosaccharide.