Premium
Chemical Synthesis of O‐Glycosylated Human Interleukin‐2 by the Reverse Polarity Protection Strategy
Author(s) -
Asahina Yuya,
Komiya Shinobu,
Ohagi Ami,
Fujimoto Rina,
Tamagaki Hiroko,
Nakagawa Katsuhiro,
Sato Takashi,
Akira Shizuo,
Takao Toshifumi,
Ishii Akira,
Nakahara Yoshiaki,
Hojo Hironobu
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201501847
Subject(s) - native chemical ligation , chemistry , isoelectric point , glycosylation , peptide , glycoprotein , polarity (international relations) , biochemistry , thioester , chemical synthesis , combinatorial chemistry , stereochemistry , cell , in vitro , enzyme
The chemical synthesis of human interleukin‐2 (IL‐2) , having a core 1 sugar, by a ligation method is reported. Although IL‐2 is a globular glycoprotein, its C‐terminal region, in particular (99‐133), is extremely insoluble when synthesized by solid‐phase method. To overcome this problem, the side‐chain carboxylic acid of the Glu residues was protected by a picolyl ester, thus reversing its polarity from negative to positive. This reverse polarity protection significantly increased the isoelectric point of the peptide segment and made it positive under acidic conditions and facilitated the purification. An efficient method to prepare the prolyl peptide thioester required for the synthesis of the (28‐65) segment was also developed. These efforts resulted in the total synthesis of the glycosylated IL‐2 having full biological activity.