title: Chemical Synthesis of O-Glycosylated Human Interleukin-2 by the Reverse Polarity Protection Strategy.
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.
authors.affiliation: Institute for Protein Research, Osaka University, Osaka 565-0871 (Japan).
authors.forename: Yuya
authors.initials: Y
authors.lastname: Asahina
authors.affiliation: Department of Applied Biochemistry, Tokai University, Kanagawa 259-1292 (Japan).
authors.forename: Shinobu
authors.initials: S
authors.lastname: Komiya
authors.affiliation: Department of Applied Biochemistry, Tokai University, Kanagawa 259-1292 (Japan).
authors.forename: Ami
authors.initials: A
authors.lastname: Ohagi
authors.affiliation: Department of Applied Biochemistry, Tokai University, Kanagawa 259-1292 (Japan).
authors.forename: Rina
authors.initials: R
authors.lastname: Fujimoto
authors.affiliation: Institute for Protein Research, Osaka University, Osaka 565-0871 (Japan).
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tamagaki
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan).
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan).
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871 (Japan).
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: Institute for Protein Research, Osaka University, Osaka 565-0871 (Japan).
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takao
authors.affiliation: Department of Applied Biochemistry, Tokai University, Kanagawa 259-1292 (Japan).
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Department of Applied Biochemistry, Tokai University, Kanagawa 259-1292 (Japan).
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakahara
authors.affiliation: Institute for Protein Research, Osaka University, Osaka 565-0871 (Japan). hojo@protein.osaka-u.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hojo
mesh_terms: D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*
chemical_list: D006023:Glycoproteins; D007376:Interleukin-2; D010455:Peptides; C050111:interleukin 2, glycosylated
keywords: glycoprotein; ligation; peptides; synthesis design; synthetic methods