title: Im10A, a short conopeptide isolated from Conus imperialis and possesses two highly concentrated disulfide bridges and analgesic activity.
abstract: In the present study, we isolated, synthesized and NMR structurally characterized a novel conopeptide Im10A consisting of 11 amino acids (NTICCEGCMCY-NH2) from Conus imperialis. Unlike other conopeptides with four cysteine residues, Im10A had only two residues in loop 1 and one residue in loop 2 (CC-loop1-C-loop2-C), which formed a stable disulfide connectivity "I-IV, II- III" (framework X) with a type I β-turn. Interestingly, Im10A exhibited 50.7% analgesic activity on rat partial sciatic nerve ligation (PNL) at 2h after Im10A administration. However, 10μM Im10A exhibited no apparent effect on neuronal nicotinic acetylcholine receptor, and it did not target DRG voltage-dependent sodium, potassium and calcium ion channels and opioid receptor. To our knowledge, Im10A had the most concentrated disulfide bridges among conopeptides with four cysteine residues. This finding provided a new motif for the future development of biomimetic compounds.
authors.affiliation: Beijing Institute of Biotechnology, Beijing 10071, PR China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yu
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, National Center for Magnetic Resonance in Wuhan, State Key laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Science, Wuhan 430071, PR China.
authors.forename: Tianpeng
authors.initials: T
authors.lastname: Du
authors.affiliation: Beijing Institute of Biotechnology, Beijing 10071, PR China.
authors.forename: Zhuguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 10071, PR China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Beijing Institute of Biotechnology, Beijing 10071, PR China.
authors.forename: Guixue
authors.initials: G
authors.lastname: Feng
authors.affiliation: Beijing Institute of Biotechnology, Beijing 10071, PR China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Dong
authors.affiliation: Beijing Institute of Biotechnology, Beijing 10071, PR China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, National Center for Magnetic Resonance in Wuhan, State Key laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Science, Wuhan 430071, PR China. Electronic address: lingjiang@wipm.ac.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Beijing Institute of Biotechnology, Beijing 10071, PR China. Electronic address: qy_dai@yahoo.com.
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Dai
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D020916:Conotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D052078:Conus Snail / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects
chemical_list: D000700:Analgesics; D020916:Conotoxins; D004220:Disulfides; D009842:Oligopeptides; D011978:Receptors, Nicotinic; D003545:Cysteine
keywords: Analgesic activity; Conopeptide; Im10A; Isolation; NMR structure; Synthesis