糖基化干扰素-γ的半合成  

Semi-synthesis of Glycosylated Interferon-γ

作　　者：周敏园 赵洁[2] 叶发荣 黄平[2] 邓明刚 王平[2] Zhou Minyuan;Zhao Jie;Ye Farong;Huang Ping;Deng Minggang;Wang Ping(College of Life Science and Technology,Huazhong Agricultural University,Wuhan 430070;Center for Chemical Glycobiology,Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,Zhangjiang Institute for Advanced Study,Shanghai Jiao Tong University,Shanghai 200240)

机构地区：[1]华中农业大学生命科学与技术学院,武汉430070 [2]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

出　　处：《有机化学》2024年第7期2296-2304,共9页Chinese Journal of Organic Chemistry

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。

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.Interferon-gamma(IFN-γ)is an important cytokine with enhanced immune activity,anti-tumor and antiviral ef-fects,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.

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 

分 类 号：TQ929.1[轻工技术与工程—发酵工程]