Chemical Synthesis of O‐Glycosylated Human Interleukin‐2 by the Reverse Polarity Protection Strategy |
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| Authors: | Dr Yuya Asahina Shinobu Komiya Ami Ohagi Rina Fujimoto Dr Hiroko Tamagaki Katsuhiro Nakagawa Dr Takashi Sato Prof?Dr Shizuo Akira Prof?Dr Toshifumi Takao Dr Akira Ishii Prof?Dr Yoshiaki Nakahara Prof?Dr Hironobu Hojo |
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| Institution: | 1. Institute for Protein Research, Osaka University, Osaka 565‐0871 (Japan);2. Department of Applied Biochemistry, Tokai University, Kanagawa 259‐1292 (Japan);3. Research Institute for Microbial Diseases, Osaka University, Osaka 565‐0871 (Japan) |
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| Abstract: | 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. |
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| Keywords: | glycoprotein ligation peptides synthesis design synthetic methods |
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