title: Interactions of Lycopodium alkaloids with acetylcholinesterase investigated by 1H NMR relaxation rate.
abstract: 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.
authors.affiliation: State Key Laboratory for Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.forename: Guowei
authors.initials: G
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Hengbin
authors.initials: H
authors.lastname: Wang
authors.forename: Shanhao
authors.initials: S
authors.lastname: Jiang
authors.forename: Dayuan
authors.initials: D
authors.lastname: Zhu
authors.forename: Weihong
authors.initials: W
authors.lastname: Du
mesh_terms: 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
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; C523525:N-acetylhuperzine A; D011807:Quinolizines; D012717:Sesquiterpenes; C523524:huperzine F; C053016:huperzine B; D006859:Hydrogen; D000110:Acetylcholinesterase