• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
ZHANGSUN Dongting, ZHU Xiaopeng, WU Yong, HU Yuanyan, BING Hui, LUO Sulan. Activities of α-conotoxin TxID isomers on human nicotinic acetylcholine receptors[J]. Journal of China Pharmaceutical University, 2016, 47(4): 483-490. DOI: 10.11665/j.issn.1000-5048.20160416
Citation: ZHANGSUN Dongting, ZHU Xiaopeng, WU Yong, HU Yuanyan, BING Hui, LUO Sulan. Activities of α-conotoxin TxID isomers on human nicotinic acetylcholine receptors[J]. Journal of China Pharmaceutical University, 2016, 47(4): 483-490. DOI: 10.11665/j.issn.1000-5048.20160416
shu

Activities of α-conotoxin TxID isomers on human nicotinic acetylcholine receptors

More Information
    Graphical Abstract
    • Abstract
  • To investigate activities of three isomers of α-conotoxin TxID on human α3β4 and α6/α3β4 nicotinic acetylcholine receptors(nAChRs). The three isomers of α-conotoxin TxID were synthesized using solid phase Fmoc chemistry and fully folded by two-step oxidations. Human α3β4 and α6/α3β4 nAChRs were expressed in oocytes of Xenopus laevis, which were used for bioassay of the three isomers, including inhibition and washout reversibility. There were obvious differences between the inhibition potency of each isomers at human α3β4 and α6/α3β4 nAChRs. The blocking was reversible and washout rapidly. The most potent isomer is the globular form with an IC50 of 9. 3 nmol/L on human α3β4 and α6/α3β4 nAChRs respectively. The 2nd potent isomer was the ribbon form with much less potency, which had an IC50 of > 5 μmol/L. The bead isomer had little or no block on human α3β4 and α6/α3β4 nAChRs with an IC50 of > 10 μmol/L. The three isomers of α-conotoxin TxID were synthesized successfully with two pairs of desired disulfide bond. Inhibition activities of the 3 isomers on human α3β4 and α6/α3β4 nAChRs were obtained respectively, which would be basis for new marine drug development of α-conotoxin TxID.
    • FullText(HTML)
    • References (24)
  • [1]
    Gotti C,Clementi F.Neuronal nicotinic receptors:from structure to pathology[J].Prog Neurobiol,2004,74(6):363-396.
    [2]
    Gotti C,Moretti M,Bohr I,et al.Selective nicotinic acetylcholine receptor subunit deficits identified in Alzheimer′s disease,Parkinson′s disease and dementia with Lewy bodies by immunoprecipitation[J].Neurobiol Dis,2006,23(2):481-489.
    [3]
    Lee CH,Huang CS,Chen CS,et al.Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells[J].J Natl Cancer Inst,2010,102(17):1322-1335.
    [4]
    Lee CH,Chang YC,Chen CS,et al.Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces alpha9-nicotinic acetylcholine receptor expression in human breast cancer cells[J].Breast Cancer Res Treat,2011,129(2):331-345.
    [5]
    Rahman S. Nicotinic receptors as therapeutic targets for drug addictive disorders[J].CNS Neurol Disord Drug Targets,2013,12(5):633-640.
    [6]
    Azam L, McIntosh JM. Alpha-conotoxins as pharmacological probes of nicotinic acetylcholine receptors[J].Acta Pharmacol Sin,2009,30(6):771-783.
    [7]
    Olivera BM,Quik M,Vincler M,et al.Subtype-selective conopeptides targeted to nicotinic receptors:concerted discovery and biomedical applications[J].Channels(Austin),2008,2(2):143-152.
    [8]
    Lebbe E K,Peigneur S,Wijesekara I,et al.Conotoxins targeting nicotinic acetylcholine receptors:an overview[J].Mar Drugs,2014,12(5):2970-3004.
    [9]
    Luo S, Zhangsun D, Zhu X, et al. Characterization of a novel alpha-conotoxin TxID from Conus textile that potently blocks rat alpha3beta4 nicotinic acetylcholine receptors[J].J Med Chem,2013,56(23):9655-9663.
    [10]
    Azam L,McIntosh JM.Molecular basis for the differential sensitivity of rat and human alpha9alpha10 nAChRs to alpha-conotoxin RgIA[J].J Neurochem,2012,122(6):1137-1144.
    [11]
    Vincler M,Wittenauer S,Parker R,et al.Molecular mechanism for analgesia involving specific antagonism of alpha9 alpha10 nicotinic acetylcholine receptors[J].Proc Natl Acad Sci U S A,2006,103(47):17880-17884.
    [12]
    Halai R, Clark RJ, Nevin ST, et al. Scanning mutagenesis of alpha-conotoxin Vc1.1 reveals residues crucial for activity at the alpha9alpha10 nicotinic acetylcholine receptor[J].J Biol Chem,2009,284(30):20275-20284.
    [13]
    McIntosh JM,Azam L,Staheli S,et al.Analogs of alpha-conotoxin MII are selective for alpha6-containing nicotinic acetylcholine receptors[J].Mol Pharmacol,2004,65(4):944-952.
    [14]
    Wu Y,Wu X,Yu J,et al.Influence of disulfide connectivity on structure and bioactivity of alpha-conotoxin TxIA[J].Molecules,2014,19(1):966-979.
    [15]
    Dutton JL,Bansal PS,Hogg RC,et al.A new level of conotoxin diversity,a non-native disulfide bond connectivity in alpha-conotoxin AuIB reduces structural definition but increases biological activity[J].J Biol Chem,2002,277(50):48849-48857.
    [16]
    Jin AH,Brandstaetter H,Nevin ST,et al.Structure of alpha-conotoxin BuIA:influences of disulfide connectivity on structural dynamics[J].BMC Struct Biol,2007,7:28.
    [17]
    Gotti C, Clementi F, Fornari A, et al. Structural and functional diversity of native brain neuronal nicotinic receptors[J].Biochem Pharmacol,2009,78(7):703-711.
    [18]
    Nicke A,Wonnacott S,Lewis RJ.Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes[J].Eur J Biochem,2004,271(12):2305-2319.
    [19]
    Kasheverov IE,Utkin YN,Tsetlin VI.Naturally occurring and synthetic peptides acting on nicotinic acetylcholine receptors[J].Curr Pharm Des,2009,15(21):2430-2452.
    [20]
    Napier IA,Klimis H,Rycroft BK,et al.Intrathecal alpha-conotoxins Vc1.1,AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain[J].Neuropharmacology, 2012,62(7):2202-2207.
    [21]
    Blyth FM,March LM,Brnabic AJ,et al.Chronic pain in Australia:a prevalence study[J].Pain,2001,89(2/3):127-134.
    [22]
    Cousins MJ,Brennan F,Carr DB.Pain relief:a universal human right[J].Pain,2004,112(1/2):1-4.
    [23]
    Eisenberg E,McNicol ED,Carr DB.Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin:systematic review and meta-analysis of randomized controlled trials[J].JAMA,2005,293(24):3043-3052.
    [24]
    Improgo MR,Soll LG,Tapper AR,et al.Nicotinic acetylcholine receptors mediate lung cancer growth[J].Front Physiol,2013,4:251.
    • Related Articles

  • Related Articles

    [1]LIU Li, LIU Zijin, TANG Jun, HE Guangwei, LIU Weizhong. Optimized synthesis process of tofacitinib citrate[J]. Journal of China Pharmaceutical University, 2022, 53(6): 685-689. DOI: 10.11665/j.issn.1000-5048.20220606
    [2]WU Xufeng, CHAI Shiying, LIU Jianhong, WANG Zhihui, YIN Ruifeng, CAO Ruiwei, SUN Xinqiang. Improvement of synthetic route of brivudine[J]. Journal of China Pharmaceutical University, 2022, 53(1): 41-45. DOI: 10.11665/j.issn.1000-5048.20220106
    [3]WANG Dong, ZHONG Jian, WANG Ling, ZHOU Zhihui, JIANG Haiting, LUO Peng, WANG Xizhi, WANG Chongyi. Improved synthetic process of apremilast[J]. Journal of China Pharmaceutical University, 2021, 52(5): 536-540. DOI: 10.11665/j.issn.1000-5048.20210504
    [4]HAN Chengqun, ZOU Qiaogen, SUN Qian, XIA Yunyan. Improvement of synthesis process of mirabegron[J]. Journal of China Pharmaceutical University, 2020, 51(4): 449-453. DOI: 10.11665/j.issn.1000-5048.20200409
    [5]ZHANG Qiuyue, YOU Qidong, YANG Jinpeng. Process improvement on the synthesis of atomoxetine[J]. Journal of China Pharmaceutical University, 2019, 50(4): 405-409. DOI: 10.11665/j.issn.1000-5048.20190404
    [6]LIU Li, WANG Chen, LIU Lixin, JI Tingting. Improved synthesis of analgesic pentazocine[J]. Journal of China Pharmaceutical University, 2018, 49(5): 568-571. DOI: 10.11665/j.issn.1000-5048.20180508
    [7]MA Li, ZHANG Menghan, XU Zhiwei, SUN Ying′ai, ZHU Jing, HUANG Yingbo, ZHANG Dayong. A new synthetic process of dapagliflozin[J]. Journal of China Pharmaceutical University, 2017, 48(1): 42-45. DOI: 10.11665/j.issn.1000-5048.20170106
    [8]WEI Qingjie, QIAO Junhua, CHEN Jianjun, GAO Zhigang, LI Yaqing. An improvement for synthesis of ceftriaxone sodium[J]. Journal of China Pharmaceutical University, 2016, 47(2): 163-165. DOI: 10.11665/j.issn.1000-5048.20160206
    [9]Improve on the Synthetic Process of Bezafibrate[J]. Journal of China Pharmaceutical University, 2003, (3): 80-81.
    [10]Improved Process of Nimodipine[J]. Journal of China Pharmaceutical University, 1998, (3): 82-83.

  • Cited by

    Periodical cited type(3)

    1. 李雨晴，邹师琪，傅伟淇，杨欣. 基于网络药理学和分子对接探讨陈皮治疗非小细胞肺癌的作用机制. 中华生物医学工程杂志. 2024(04): 266-272 .
    2. 高杰，丁留成，卫中庆. 脂质代谢在去势抵抗性前列腺癌中的研究进展. 东南国防医药. 2021(02): 169-174 .
    3. 赵帅华，董卫红，杨敬，韩保卫. ABHD5过表达对结肠癌细胞侵袭、迁移及AMPK/mTOR通路的影响. 中国普外基础与临床杂志. 2021(07): 850-855 .

    Other cited types(2)

Catalog

    Get Citation
    PDF
    XML
    Article views (785) PDF downloads (1596) Cited by(5)
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：366149

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return