title: Total synthesis of mambalgin-1/2/3 by two-segment hydrazide-based native chemical ligation.
abstract: Mambalgins are a class of 57-residue polypeptide toxins isolated from the venom of the African mamba. They exhibit potent analgesic effects by inhibiting the acid-sensing ion channels. Classified as members of the family of three-finger toxins, mambalgins contain four pairs of disulfide bridges that help to stabilize the three-finger scaffold. Here, we report the chemical synthesis of functional mambalgin-1/2/3 by using one-step two-segment hydrazide-based native chemical ligation. The two-segment 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 © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.|Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Lan
authors.affiliation: IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.|School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
authors.forename: Man
authors.initials: M
authors.lastname: Pan
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.|Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Gao
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Zheng
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, China.
authors.forename: Ji-Shen
authors.initials: JS
authors.lastname: Zheng
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei, 230009, China.|State Key Laboratory of Medicinal Chemical Biology, Nankai University, Nankai, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.|School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Bailong
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.|Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D001386:Azides / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D004546:Elapid Venoms / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001386:Azides; D004220:Disulfides; D004546:Elapid Venoms; D010455:Peptides
keywords: acid-sensing ion channels; mambalgins; native chemical ligation; peptide hydrazides; toxin