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They exhibit potent analgesic effects by inhibiting the acid\u2010sensing ion channels. Classified as members of the family of three\u2010finger toxins, mambalgins contain four pairs of disulfide bridges that help to stabilize the three\u2010finger scaffold. Here, we report the chemical synthesis of functional mambalgin\u20101\/2\/3 by using one\u2010step two\u2010segment hydrazide\u2010based native chemical ligation. The two\u2010segment ligation approach reported here may enable efficient production of mambalgin toxins. These synthetic mambalgins are useful compounds for development of diagnostic or therapeutic reagents. Copyright \u00a9 2016 European Peptide Society and John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/psc.2868","type":"journal-article","created":{"date-parts":[[2016,3,19]],"date-time":"2016-03-19T01:19:48Z","timestamp":1458350388000},"page":"320-326","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Total synthesis of mambalgin\u20101\/2\/3 by two\u2010segment hydrazide\u2010based native chemical ligation"],"prefix":"10.1002","volume":"22","author":[{"given":"Huan","family":"Lan","sequence":"first","affiliation":[{"name":"Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology (Ministry of Education), Department of Chemistry Tsinghua University  Beijing 100084 China"},{"name":"Tsinghua\u2010Peking Center for Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wu","sequence":"additional","affiliation":[{"name":"IDG\/McGovern Institute for Brain Research, School of Pharmaceutical Sciences Tsinghua University  Beijing 100084 China"},{"name":"School of Pharmaceutical Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zheng","sequence":"additional","affiliation":[{"name":"High Magnetic Field Laboratory, Chinese Academy of Sciences  Hefei 230031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology (Ministry of Education), Department of Chemistry Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chao","family":"Huang","sequence":"additional","affiliation":[{"name":"Tsinghua\u2010Peking Center for Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology (Ministry of Education), Department of Chemistry Tsinghua University  Beijing 100084 China"},{"name":"Tsinghua\u2010Peking Center for Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Yun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Tsinghua\u2010Peking Center for Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Shen","family":"Zheng","sequence":"additional","affiliation":[{"name":"High Magnetic Field Laboratory, Chinese Academy of Sciences  Hefei 230031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Ming","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medical Engineering Hefei University of Technology  Hefei 230009 China"},{"name":"State Key Laboratory of Medicinal Chemical Biology Nankai University  Nankai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailong","family":"Xiao","sequence":"additional","affiliation":[{"name":"IDG\/McGovern Institute for Brain Research, School of Pharmaceutical Sciences Tsinghua University  Beijing 100084 China"},{"name":"School of Pharmaceutical Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology (Ministry of Education), Department of Chemistry Tsinghua University  Beijing 100084 China"},{"name":"Tsinghua\u2010Peking Center for Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"693","article-title":"Acid\u2010sensing ion channels: a new target for pain and CNS diseases","volume":"12","author":"Sluka K","year":"2009","journal-title":"Curr. 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