Interactions of Lycopodium alkaloids with acetylcholinesterase investigated by 1H NMR relaxation rate.
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.
Li
Yiming
Y
State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201203, China.
Yin
Guowei
G
Wei
Wei
W
Wang
Hengbin
H
Jiang
Shanhao
S
Zhu
Dayuan
D
Du
Weihong
W
D000110:Acetylcholinesterase / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D032502:Lycopodium / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011807:Quinolizines / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; C523525:N-acetylhuperzine A; D011807:Quinolizines; D012717:Sesquiterpenes; C523524:huperzine F; C053016:huperzine B; D006859:Hydrogen; D000110:Acetylcholinesterase