Chemical Synthesis of glycoproteins having complex type oligosaccharides and elucidation of oligosaccharide functions

为了阐明低聚糖的功能，对均相糖蛋白的化学合成进行了研究。为了合成目标糖蛋白，我们设计了全长的糖基多肽链，并将其分成几个片段，并用改进的、安全的tert-Boc-SPPS制备。由此获得的糖肽- α -硫酯和肽- α -硫酯通过重复的天然化学连接成功偶联。随后的化学合成均质糖肽的折叠实验得到了正确折叠的具有天然二硫键模式的糖蛋白。用这种方法成功地合成了促红细胞生成素、趋化因子和凝集素。

In order to elucidate oligosaccharide functions, chemical synthesis of homogeneous glycoprotein was examined. For the synthesis of target glycoproteins, full-length glycosylpolypeptide chains was designed to divide into several segments and these were prepared by our improved and safe tert-Boc-SPPS. Glycopeptide-alpha-thioester and peptide-alpha-thioesters thus obtained were successfully coupled by repetitive native chemical ligation. Subsequent folding experiments of chemically synthesized homogeneous glycopeptide yielded correctly folded glycoproteins with native disulfide bond patterns. Using this method, erythropoietin, chemokine and lectin were successfully synthesized.