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糖基化干扰素-γ的半合成
Semi-synthesis of Glycosylated Interferon-γ
【摘要】 干扰素-γ(IFN-γ)是一种重要的细胞因子,具有增强免疫活性、抗肿瘤和抗病毒的作用,在医学研究和临床应用中具有广泛的潜力.本研究报道了一种均一N-Glc NAc修饰的IFN-γ的化学半合成方法.利用化学方法合成制备糖肽片段(Pyr1-Leu33)和多肽片段(Lys34-Ser39),并通过大肠杆菌表达得到多肽片段(Ser40-Gly138).采用“表达丝氨酸连接”和“自然化学连接-脱硫”相结合的策略,成功完成了自C端到N端的N-Glc NAc修饰的IFN-γ蛋白的合成,并成功地对目标糖蛋白进行了复性.
【Abstract】 Interferon-gamma(IFN-γ) is an important cytokine with enhanced immune activity, anti-tumor and antiviral effects, and holds significant potential in medical research and clinical applications. In this study, we report a highly efficient semi-synthesis strategy of homogeneous N-Glc NAc modified IFN-γ. The glycopeptide fragment(Pyr1-Leu33) and peptide fragment(Lys34-Ser39) were prepared through chemical methods. And the peptide fragment(Ser40-Gly138) was obtained through Escherichia coli(E. coli) expression. Subsequently, using a combination of “expressed serine ligation” and “native chemical ligation-desulfurization”, we ligated these fragments from the C-terminal to the N-terminal, resulting in a full-length glycoprotein, which was successfully refolded to obtain the desired product.
【Key words】 native chemical ligation; expressed serine ligation; β-thioamino acid; glycosylation;
- 【文献出处】 有机化学 ,Chinese Journal of Organic Chemistry , 编辑部邮箱 ,2024年07期
- 【分类号】TQ929.1
- 【下载频次】11