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糖基化干扰素-γ的半合成

Semi-synthesis of Glycosylated Interferon-γ

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【作者】 周敏园; 赵洁; 叶发荣; 黄平; 邓明刚; 王平;

【Author】 Zhou Minyuan;Zhao Jie;Ye Farong;Huang Ping;Deng Minggang;Wang Ping;College of Life Science and Technology,Huazhong Agricultural University;Center for Chemical Glycobiology,Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,Zhangjiang Institute for Advanced Study,Shanghai Jiao Tong University;

【通讯作者】 邓明刚;王平;

【机构】 华中农业大学生命科学与技术学院; 上海交通大学张江高等研究院上海手性药物分子工程重点实验室化学糖生物学中心;

【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.

【基金】 国家自然科学基金(Nos.21672146,22077080,92253302);上海交通大学医工交叉基金(No.21TQ1400210)资助项目~~
  • 【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
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