title: Chemical synthesis of homogeneous human glycosyl-interferon-β that exhibits potent antitumor activity in vivo.
abstract: Chemical synthesis of homogeneous human glycoproteins exhibiting bioactivity in vivo has been a challenging task. In an effort to overcome this long-standing problem, we selected interferon-β and examined its synthesis. The 166 residue polypeptide chain of interferon-β was prepared by covalent condensation of two synthetic peptide segments and a glycosylated synthetic peptide bearing a complex-type glycan of biological origin. The peptides were covalently condensed by native chemical ligation. Selective desulfurization followed by deprotection of the two Cys(Acm) residues gave the target full-length polypeptide chain of interferon-β bearing either a complex-type sialyl biantennary oligosaccharide or its asialo form. Subsequent folding with concomitant formation of the native disulfide bond afforded correctly folded homogeneous glycosyl-interferon-β. The chemically synthesized sialyl interferon-β exhibited potent antitumor activity in vivo.
authors.affiliation: Glycotechnology Laboratory, Otsuka Chemical Co, Ltd, Shimogyo-ku, Kyoto, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Sakamoto
authors.forename: Katsunari
authors.initials: K
authors.lastname: Tezuka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Fukae
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishii
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taduru
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Maeda
authors.forename: Masaki
authors.initials: M
authors.lastname: Ouchi
authors.forename: Kenta
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nambu
authors.forename: Jun
authors.initials: J
authors.lastname: Igarashi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kajihara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D016899:Interferon-beta / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016899:Interferon-beta