Li Yiming, Yin Guowei, Wei Wei, Wang Hengbin, Jiang Shanhao, Zhu Dayuan, Du Weihong
State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201203, China.
Biophys Chem. 2007 Sep;129(2-3):212-7. doi: 10.1016/j.bpc.2007.05.020. Epub 2007 Jun 7.
In order to further understand the interaction processes between the Lycopodium alkaloids and acetylcholinesterase, the binding properties of N-acetyl huperzine A (1), huperzine B (2) and huperzine F (3) with Torpediniforms Nacline acetylcholinesterase (TnAchE) were investigated by 1H NMR methods. The nonselective, selective and double-selective spin-lattice relaxation rates were acquired in the absence and presence of TnAchE at a ratio of [ligand]/[protein]=1:0.005. The selective relaxation rates show protons of 1-3 have dipole-dipole interaction with protons of TnAchE at the binding interface. The molecular rotational correlation time of bound ligands was calculated by double-selective relaxation rate at 298 K, which showed that 1-3 had high affinity with the protein. The results indicate that investigation of 1H NMR relaxation data is a useful method to locate the new Lycopodium alkaloids as AchE inhibitors.
为了进一步了解石松生物碱与乙酰胆碱酯酶之间的相互作用过程，采用1H NMR方法研究了N-乙酰石杉碱甲（1）、石杉碱乙（2）和石杉碱F（3）与电鳐乙酰胆碱酯酶（TnAchE）的结合特性。在不存在和存在TnAchE的情况下，以[配体]/[蛋白质]=1:0.005的比例获得非选择性、选择性和双选择性自旋晶格弛豫率。选择性弛豫率表明，1-3的质子与结合界面处TnAchE的质子存在偶极-偶极相互作用。通过298 K下的双选择性弛豫率计算了结合配体的分子旋转相关时间，结果表明1-3与该蛋白具有高亲和力。结果表明，研究1H NMR弛豫数据是定位新型石松生物碱作为乙酰胆碱酯酶抑制剂的一种有用方法。
