Chemical Synthesis of Homogeneous Human Glycosyl-interferon-尾 That Exhibits Potent Antitumor Activity in Vivo

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• 作者：Izumi Sakamoto ; Katsunari Tezuka ; Kazuhiro Fukae ; Kazuyuki Ishii ; Keisuke Taduru ; Masatoshi Maeda ; Masaki Ouchi ; Kenta Yoshida ; Yuri Nambu ; Jun Igarashi ; Naohiro Hayashi ; Takashi Tsuji ; Yasuhiro Kajihara
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：March 28, 2012
• 年：2012
• 卷：134
• 期：12
• 页码：5428-5431
• 全文大小：298K
• 年卷期：v.134,no.12(March 28, 2012)
• ISSN：1520-5126

文摘

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-尾 and examined its synthesis. The 166 residue polypeptide chain of interferon-尾 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-尾 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-尾. The chemically synthesized sialyl interferon-尾 exhibited potent antitumor activity in vivo.