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化学学报
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化学学报 ›› 2007, Vol. 65 ›› Issue (5): 415-420. 上一篇    下一篇

研究论文

应用1H NMR弛豫观察石杉碱戊与乙酰胆碱酯酶的结合

杜为红†,*,1,2, 李医明†,3, 甘秋玲2, 蒋山好3, 谭昌恒3, 朱大元3   

  1. (1中国人民大学化学系 北京 100872)
    (2北京师范大学化学系 北京 100875)
    (3中国科学院上海药物研究所 上海 201203)
  • 投稿日期:2006-06-19 修回日期:2006-07-20 发布日期:2007-03-14
  • 通讯作者: 杜为红

1H NMR Relaxation Investigation of Huperzine E Binding to Acetylcholinesterase

DU Wei-Hong†,*,1,2; LI Yi-Ming†,3; GAN Qiu-Ling2; JIANG Shan-Hao3; TAN Chang-Heng3; ZHU Da-Yuan3   

  1. (1 Department of Chemistry, Renmin University of China, Beijing 100872)
    (2 Department of Chemistry, Beijing Normal University, Beijing 100875)
    (3 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203)
  • Received:2006-06-19 Revised:2006-07-20 Published:2007-03-14

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为筛选更好的乙酰胆碱酯酶抑制剂, 应用1H NMR的方法研究了石杉碱甲的一个类似物——石杉碱戊与乙酰胆碱酯酶的结合性质, 获得了加乙酰胆碱酯酶([配体]∶[蛋白]＝1∶0.005)和不加酶时石杉碱戊部分质子的非选择性、单选择性和双选择性的自旋晶格弛豫速率. 加酶后质子的选择性弛豫速率变化较大, 在T＝298 K时石杉碱戊的H-1a/H-1b质子对的分子运动相关时间τ1a,1b由不加酶时的27.7 ps变化到结合酶后的11.7 ns, H-2/H-3质子对的分子运动相关时间τ2,3由35.2 ps变化到9.46 ns, 由此得出石杉碱戊与乙酰胆碱酯酶有较强的结合作用.

关键词: 石杉碱戊, 乙酰胆碱酯酶, 质子自旋-晶格弛豫速率, 分子运动相关时间, 核磁共振

In order to search for better acetylcholinesterase (AchE) inhibitors, the binding properties of AchE with huperizine E, which is a derivative of huperzine A, were investigated by 1H NMR methods. The nonselective, selective and double-selective spin-lattice relaxation rates of some protons in huperzine E were acquired in the absence and presence of AchE at a concentration ratio of [ligand]∶[protein]＝1∶0.005. The enhancements of selective relaxation rates of these protons were obvious after adding AchE. The molecular motional correlation times of two pairs of protons, H-1a/H-1b and H-2/H-3, in the bound state at T＝298 K were 11.7 and 9.46 ns respectively, while they were 27.7 and 35.2 ps in the free state. All of these show that Huperzine E has high binding affinity with AchE.

Key words: huperzine E, acetylcholinesterase, proton spin-lattice relaxation rate, molecular motional correlation time, NMR