Chemical Synthesis of Homogeneous Human Glycosyl-interferon-β That Exhibits Potent Antitumor Activity in Vivo
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 conde...
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| Veröffentlicht in: | Journal of the American Chemical Society 2012-03, Vol.134 (12), p.5428-5431 |
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| container_title | Journal of the American Chemical Society |
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| creator | Sakamoto, Izumi Tezuka, Katsunari Fukae, Kazuhiro Ishii, Kazuyuki Taduru, Keisuke Maeda, Masatoshi Ouchi, Masaki Yoshida, Kenta Nambu, Yuri Igarashi, Jun Hayashi, Naohiro Tsuji, Takashi Kajihara, Yasuhiro |
| description | 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. |
| doi_str_mv | 10.1021/ja2109079 |
| format | Article |
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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.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/ja2109079</identifier><identifier>PMID: 22404596</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amino Acid Sequence ; Animals ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - therapeutic use ; Cell Line ; Cell Proliferation - drug effects ; Glycosylation ; Humans ; Interferon-beta - chemical synthesis ; Interferon-beta - chemistry ; Interferon-beta - therapeutic use ; Mice ; Models, Molecular ; Molecular Sequence Data ; Neoplasms - drug therapy ; Xenograft Model Antitumor Assays</subject><ispartof>Journal of the American Chemical Society, 2012-03, Vol.134 (12), p.5428-5431</ispartof><rights>Copyright © 2012 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a314t-c863e910e46555abedb54597edc6c552e278c68870f6a19cb1a357afc6a0fb0b3</citedby><cites>FETCH-LOGICAL-a314t-c863e910e46555abedb54597edc6c552e278c68870f6a19cb1a357afc6a0fb0b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/ja2109079$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ja2109079$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27078,27926,27927,56740,56790</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22404596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sakamoto, Izumi</creatorcontrib><creatorcontrib>Tezuka, Katsunari</creatorcontrib><creatorcontrib>Fukae, Kazuhiro</creatorcontrib><creatorcontrib>Ishii, Kazuyuki</creatorcontrib><creatorcontrib>Taduru, Keisuke</creatorcontrib><creatorcontrib>Maeda, Masatoshi</creatorcontrib><creatorcontrib>Ouchi, Masaki</creatorcontrib><creatorcontrib>Yoshida, Kenta</creatorcontrib><creatorcontrib>Nambu, Yuri</creatorcontrib><creatorcontrib>Igarashi, Jun</creatorcontrib><creatorcontrib>Hayashi, Naohiro</creatorcontrib><creatorcontrib>Tsuji, Takashi</creatorcontrib><creatorcontrib>Kajihara, Yasuhiro</creatorcontrib><title>Chemical Synthesis of Homogeneous Human Glycosyl-interferon-β That Exhibits Potent Antitumor Activity in Vivo</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>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.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Cell Line</subject><subject>Cell Proliferation - drug effects</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Interferon-beta - chemical synthesis</subject><subject>Interferon-beta - chemistry</subject><subject>Interferon-beta - therapeutic use</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Neoplasms - drug therapy</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkM9KwzAcx4MoOqcHX0ByEfFQTdImbY9jzE0QFJxeS5r96jLaRJN02NfyQXwmq5s7efrxgw_ffwidUXJNCaM3K8koyUma76EB5YxEnDKxjwaEEBalmYiP0LH3q_5NWEYP0RFjCUl4LgbIjJfQaCVr_NSZsASvPbYVntnGvoIB23o8axtp8LTulPVdHWkTwFXgrIm-PvF8KQOefCx1qYPHjzaACXhkgg5tYx0eqaDXOnRYG_yi1_YEHVSy9nC6vUP0fDuZj2fR_cP0bjy6j2RMkxCpPjPklEAiOOeyhEXJ-7wpLJRQnDNgaaZElqWkEpLmqqQy5qmslJCkKkkZD9HlRvfN2fcWfCga7RXUtfztVOQiTnJGe5shutqQylnvHVTFm9ONdF1BSfGzbrFbt2fPt6pt2cBiR_7N2QMXG0AqX6xs60xf8h-hb1G9gnk</recordid><startdate>20120328</startdate><enddate>20120328</enddate><creator>Sakamoto, Izumi</creator><creator>Tezuka, Katsunari</creator><creator>Fukae, Kazuhiro</creator><creator>Ishii, Kazuyuki</creator><creator>Taduru, Keisuke</creator><creator>Maeda, Masatoshi</creator><creator>Ouchi, Masaki</creator><creator>Yoshida, Kenta</creator><creator>Nambu, Yuri</creator><creator>Igarashi, Jun</creator><creator>Hayashi, Naohiro</creator><creator>Tsuji, Takashi</creator><creator>Kajihara, Yasuhiro</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120328</creationdate><title>Chemical Synthesis of Homogeneous Human Glycosyl-interferon-β That Exhibits Potent Antitumor Activity in Vivo</title><author>Sakamoto, Izumi ; Tezuka, Katsunari ; Fukae, Kazuhiro ; Ishii, Kazuyuki ; Taduru, Keisuke ; Maeda, Masatoshi ; Ouchi, Masaki ; Yoshida, Kenta ; Nambu, Yuri ; Igarashi, Jun ; Hayashi, Naohiro ; Tsuji, Takashi ; Kajihara, Yasuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a314t-c863e910e46555abedb54597edc6c552e278c68870f6a19cb1a357afc6a0fb0b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Cell Line</topic><topic>Cell Proliferation - drug effects</topic><topic>Glycosylation</topic><topic>Humans</topic><topic>Interferon-beta - chemical synthesis</topic><topic>Interferon-beta - chemistry</topic><topic>Interferon-beta - therapeutic use</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Neoplasms - drug therapy</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakamoto, Izumi</creatorcontrib><creatorcontrib>Tezuka, Katsunari</creatorcontrib><creatorcontrib>Fukae, Kazuhiro</creatorcontrib><creatorcontrib>Ishii, Kazuyuki</creatorcontrib><creatorcontrib>Taduru, Keisuke</creatorcontrib><creatorcontrib>Maeda, Masatoshi</creatorcontrib><creatorcontrib>Ouchi, Masaki</creatorcontrib><creatorcontrib>Yoshida, Kenta</creatorcontrib><creatorcontrib>Nambu, Yuri</creatorcontrib><creatorcontrib>Igarashi, Jun</creatorcontrib><creatorcontrib>Hayashi, Naohiro</creatorcontrib><creatorcontrib>Tsuji, Takashi</creatorcontrib><creatorcontrib>Kajihara, Yasuhiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakamoto, Izumi</au><au>Tezuka, Katsunari</au><au>Fukae, Kazuhiro</au><au>Ishii, Kazuyuki</au><au>Taduru, Keisuke</au><au>Maeda, Masatoshi</au><au>Ouchi, Masaki</au><au>Yoshida, Kenta</au><au>Nambu, Yuri</au><au>Igarashi, Jun</au><au>Hayashi, Naohiro</au><au>Tsuji, Takashi</au><au>Kajihara, Yasuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemical Synthesis of Homogeneous Human Glycosyl-interferon-β That Exhibits Potent Antitumor Activity in Vivo</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2012-03-28</date><risdate>2012</risdate><volume>134</volume><issue>12</issue><spage>5428</spage><epage>5431</epage><pages>5428-5431</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><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.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>22404596</pmid><doi>10.1021/ja2109079</doi><tpages>4</tpages></addata></record> |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Amino Acid Sequence Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - therapeutic use Cell Line Cell Proliferation - drug effects Glycosylation Humans Interferon-beta - chemical synthesis Interferon-beta - chemistry Interferon-beta - therapeutic use Mice Models, Molecular Molecular Sequence Data Neoplasms - drug therapy Xenograft Model Antitumor Assays |
| title | Chemical Synthesis of Homogeneous Human Glycosyl-interferon-β That Exhibits Potent Antitumor Activity in Vivo |
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