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2024 , Vol. 44 >Issue 7: 2296 - 2304

DOI: https://doi.org/10.6023/cjoc202402006

研究论文

糖基化干扰素-γ的半合成

  • 周敏园 ,
  • 赵洁 ,
  • 叶发荣 ,
  • 黄平 ,
  • 邓明刚 ,
  • 王平
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  • a 华中农业大学生命科学与技术学院 武汉 430070
    b 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 上海 200240
† 共同第一作者.

收稿日期: 2024-02-05

  修回日期: 2024-03-17

  网络出版日期: 2024-04-10

基金资助

国家自然科学基金(21672146); 国家自然科学基金(22077080); 国家自然科学基金(92253302); 上海交通大学医工交叉基金(21TQ1400210)

收起

Semi-synthesis of Glycosylated Interferon-γ

  • Minyuan Zhou ,
  • Jie Zhao ,
  • Farong Ye ,
  • Ping Huang ,
  • Minggang Deng ,
  • Ping Wang
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  • a College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070
    b Center for Chemical Glycobiology, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 200240
† These authors contributed equally to this work.
* E-mail: ;

Received date: 2024-02-05

  Revised date: 2024-03-17

  Online published: 2024-04-10

Supported by

National Natural Science Fund(21672146); National Natural Science Fund(22077080); National Natural Science Fund(92253302); Cross Fund of Shanghai Jiao Tong University Medical Engineering(21TQ1400210)

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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-GlcNAc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-GlcNAc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.

关键词： 自然化学连接; 表达丝氨酸连接; β-硫代氨基酸; 糖基化修饰

本文引用格式

周敏园 , 赵洁 , 叶发荣 , 黄平 , 邓明刚 , 王平 . 糖基化干扰素-γ的半合成[J]. 有机化学, 2024 , 44(7) : 2296 -2304 . DOI: 10.6023/cjoc202402006

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-GlcNAc 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

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