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Chemical synthesis and characterization of two α4/7-conotoxins
  • ISSN号:1672-9145
  • 期刊名称:《生物化学与生物物理学报:英文版》
  • 时间:0
  • 分类:Q781[生物学—分子生物学] TQ464.9[化学工程—制药化工]
  • 作者机构:[1]Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai 200092, China, [2]Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine (SCSB), Shanghai Jiao Tong University, Shanghai 200240, China, [3]Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA, [4]Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
  • 相关基金:This work was supported by the grants from National Basic Research Program of China (2010CB529802), Chinese Academy of Sciences for Key Topics in Innovation Engineering (KSCX2-YWR-104), and NIH Foundation (NIH R01 GM32629).
中文摘要:

-Conotoxins 是对烟碱的醋胆素受体(nAChRs ) 的特定的子类型作为有势力和选择对手起作用的小抑制二硫化物的肽。我们以前从食虫的 Conus leopardus 从 molluscivorous Conus marmoreus 和 Lp1.4 克隆二 -conotoxins, Mr1.1。他们俩有 -conotoxins 的亚科的典型 4/7-type 框架 neuronal nAChRs 上的那行为。在这个工作,我们化学上综合了这二毒素并且描绘了他们的功能的性质。合成 Mr1.1 能首先禁止唤起的醋胆素(ACh ) 水流 reversibly 在表示卵母细胞的老鼠 7 nAChR,而 Lp1.4 是老鼠的意外特定的 blocker 胎儿的肌肉 11 受体。尽管他们的抑制亲密关系是相对低的,他们的唯一的受体识别侧面为毒素受体相互作用研究使他们成为珍贵工具。Mr1.1 能也压制煽动性的反应在 vivo 伤害,建议它应该进一步关于它在为疼痛的治疗的痛觉缺失和它的机制或治疗学的目标的分子的角色被调查。

英文摘要:

α-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors (nAChRs). We previously cloned two α-conotoxins, Mrl.1 from the molluscivorous Conus marmoreus and Lpl.4 from the vermivorous Conus leopardus. Both of them have the typical 4/7-type framework of the subfamily of α-conotoxins that act on neuronal nAChRs. In this work, we chemically synthesized these two toxins and characterized their functional properties. The synthetic Mrl.1 could primarily inhibit acetylcholine (ACh)-evoked currents reversibly in the oocyte-expressed rat α7 nAChR, whereas Lpl.4 was an unexpected specific blocker of the mouse fetal muscle α1β1γδ receptor. Although their inhibition affinities were relatively low, their unique receptor recognition profiles make them valuable tools for toxin-receptor interaction studies. Mr1.1 could also suppress the inflammatory response to pain in vivo, suggesting that it should be further investigated with respect to its molecular role in analgesia and its mechanism or therapeutic target for the treatment of pain.

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期刊信息
  • 《生物化学与生物物理学报:英文版》
  • 北大核心期刊(2004版)
  • 主管单位:
  • 主办单位:中国科学院上海生物化学研究所
  • 主编:
  • 地址:上海岳阳路319号
  • 邮编:200031
  • 邮箱:abbs@sibs.ac.cn
  • 电话:021-54920956 54920955
  • 国际标准刊号:ISSN:1672-9145
  • 国内统一刊号:ISSN:31-1940/Q
  • 邮发代号:4-210
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  • 美国化学文摘(网络版),英国农业与生物科学研究中心文摘,荷兰文摘与引文数据库,美国生物医学检索系统,美国剑桥科学文摘,美国科学引文索引(扩展库),美国生物科学数据库,英国动物学记录,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),英国英国皇家化学学会文摘,中国北大核心期刊(2000版)
  • 被引量:5851