Revealing Functional Significance of Interleukin-2 Glycopro-teoforms Enabled by Expressed Serine Ligation  

作　　者：Jie Zhao Jiazhi Liu Xinnan Liu Qi Cao Hongbo Zhao Lizhen Liu Farong Ye Can Wang Hong Shao Dongxiang Xue Houchao Tao Bin Li Biao Yu Ping Wang 

机构地区：[1]Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,800 Dongchuan Road,Shanghai 200240,China [2]Shanghai Institute of Immunology,Department of Immunology and Microbiology,Shanghai Jiao Tong University School of Medicine,280 S.Chongqing Road,Shanghai 200025,China [3]Obstetrics and Gynecology Hospital of Fudan University,Shanghai 200011,China [4]Shanghai Institute for Food and Drug Control,NMPA Key Laboratory for Quality Control of Therapeutic Monoclonal Antibodies,Shanghai 201203,China [5]iHuman Institute,ShanghaiTech University,Haike Road 230,Shanghai 200032,China [6]State Key Laboratory of Bioorganic and Natural Products Chemistry,Center for Excellence in Molecular Synthesis,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,345 Lingling Road,Shanghai 200032

出　　处：《Chinese Journal of Chemistry》2022年第7期787-793,共7页中国化学（英文版）

基　　金：supported by the National Natural Science Foundation of China(22077080,21907064 and 22107068);Special Projects of the Central Government in Guidance of Local Science and Technology Development(2021Szvup077).

摘　　要：Naturally occurring interleukin-2(IL-2)is a pleiotropic glycoprotein that regulates immune responses by controlling the differentia-tion and homeostasis of T cells.Non-glycosylated IL-2 has been used in clinical settings for three decades.However,the function of the O-glycan of native IL-2 remains elusive.Herein,to stress this issue,we report a highly efficient semi-synthesis of homogeneous glycosylated IL-2 with various glycoproteoforms on a multi-milligram scale.The glycopeptide fragment was prepared by chemical synthesis and then merged with recombinant fragment via a serine ligation to generate the desired glycoprotein in a single opera-tion.Biological evaluation of the homogenous glycoprotein library reveals that the activity of IL-2 in activating individual T cell subset is glycan dependent,thus highlighting the possibility of further improving current clinical medicine.

关 键 词：OLIGOSACCHARIDE GLYCOPROTEIN Serine ligation INTERLEUKIN-2 GLYCOPEPTIDES 

分 类 号：R3[医药卫生—基础医学]