Li Yiming, Li Qian, Sun Manchi, Song Guoqiang, Jiang Shanhao, Zhu Dayuan
State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Bioorg Med Chem Lett. 2004 Mar 22;14(6):1585-8. doi: 10.1016/j.bmcl.2003.12.055.
The binding properties of huperzine A (1) with Torpediniforms Nacline acetylcholinesterase (TnAChE) were investigated by (1)H NMR methods. The noselective, selective and double-selective spin-lattice relaxation rates were acquired in absent and present of TnAChE at a ratio [ligand]/[protein]=1:0.005. The selective relaxation rates shown protons of 1 had dipole-dipole interaction with protein active site protons. The motional correlation time of bound ligand was calculated by double-selective relaxation rate at 1 tau(2,3)=40.5 ns at 298 K, which showed 1 had high affinity with TnAChE. The experiments give a possible method to use TnAChE to locate the new huperzine A derivatives as AChE inhibitors.
采用¹H NMR方法研究了石杉碱甲（1）与电鳐乙酰胆碱酯酶（TnAChE）的结合特性。在配体/蛋白质比例为1:0.005的情况下，分别在不存在和存在TnAChE时获得了非选择性、选择性和双选择性自旋晶格弛豫率。选择性弛豫率表明1的质子与蛋白质活性部位的质子存在偶极 - 偶极相互作用。通过双选择性弛豫率计算出结合配体在298K时的运动相关时间为τ(2,3)=40.5 ns，这表明1与TnAChE具有高亲和力。这些实验为利用TnAChE来定位新型石杉碱甲衍生物作为乙酰胆碱酯酶抑制剂提供了一种可能的方法。
