Revealing Functional Significance of Interleukin‐2 Glycoproteoforms Enabled by Expressed Serine Ligation
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
Abstract
Comprehensive Summary Naturally occurring interleukin‐2 (IL‐2) is a pleiotropic glycoprotein that regulates immune responses by controlling the differentiation 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 operation. 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.