糖基化干扰素-γ的半合成

Semi-synthesis of Glycosylated Interferon-γ

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.