Lee BH

References (16)

Title : Clinical Application of Whole Exome Sequencing to Identify Rare but Remediable Neurologic Disorders - Kim_2020_J.Clin.Med_9_3724
Author(s) : Kim MJ , Yum MS , Seo GH , Lee Y , Jang HN , Ko TS , Lee BH
Ref : J Clin Med , 9 : , 2020
Abstract : BACKGROUND: The aim of this study was to describe the application of whole exome sequencing (WES) in the accurate genetic diagnosis and personalized treatment of extremely rare neurogenetic disorders. METHODS: From 2017 to 2019, children with neurodevelopmental symptoms were evaluated using WES in the pediatric neurology clinic and medical genetics center. The clinical presentation, laboratory findings including the genetic results from WES, and diagnosis-based treatment and outcomes of the four patients are discussed. RESULTS: A total of 376 children with neurodevelopmental symptom were evaluated by WES, and four patients (1.1%) were diagnosed with treatable neurologic disorders. Patient 1 (Pt 1) showed global muscle hypotonia, dysmorphic facial features, and multiple anomalies beginning in the perinatal period. Pt 1 was diagnosed with congenital myasthenic syndrome 22 of PREPL deficiency. Pt 2 presented with hypotonia and developmental arrest and was diagnosed with autosomal recessive dopa-responsive dystonia due to TH deficiency. Pt 3, who suffered from intractable epilepsy and progressive cognitive decline, was diagnosed with epileptic encephalopathy 47 with a heterozygous FGF12 mutation. Pt 4 presented with motor delay and episodic ataxia and was diagnosed with episodic ataxia type II (heterozygous CACNA1A mutation). The patients' major neurologic symptoms were remarkably relieved with pyridostigmine (Pt 1), levodopa (Pt 2), sodium channel blocker (Pt 3), and acetazolamide (Pt 4), and most patients regained developmental milestones in the follow-up period (0.4 to 3 years). CONCLUSIONS: The early application of WES helps in the identification of extremely rare genetic diseases, for which effective treatment modalities exist. Ultimately, WES resulted in optimal clinical outcomes of affected patients.
ESTHER : Kim_2020_J.Clin.Med_9_3724
PubMedSearch : Kim_2020_J.Clin.Med_9_3724
PubMedID: 33233562
Gene_locus related to this paper: human-PREPL

Title : Undibacterium piscinae sp. nov., isolated from Korean shiner intestine - Lee_2019_Int.J.Syst.Evol.Microbiol_69_3148
Author(s) : Lee SY , Kang W , Kim PS , Kim HS , Sung H , Shin NR , Whon TW , Yun JH , Lee JY , Jung MJ , Jeong YS , Tak EJ , Han JE , Hyun DW , Kang MS , Lee KE , Lee BH , Bae JW
Ref : Int J Syst Evol Microbiol , 69 :3148 , 2019
Abstract : A novel Gram-stain-negative, non-spore-forming, obligate aerobic, motile, rod-shaped, and flagellated bacterium, designated S11R28(T), was isolated from the intestinal tract of a Korean shiner, Coreoleuciscus splendidus. Based on 16S rRNA gene sequences, strain S11R28(T) was identified as member of the genus Undibacterium in class Betaproteobacteria, and was closely related to Undibacterium parvum DSM 23061(T) (98.49%). The isolate grew at 4-25 degreesC, pH 6-9, with 0% (w/v) NaCl, and grew optimally at 20 degreesC, pH 8, in the absence of NaCl. The main cellular fatty acids were C(16:0) and summed features 3 (C(16:1)omega7c and/or C(16:1)omega6c). The strain possessed diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine as predominant polar lipids, and ubiquinone Q-8 as a respiratory quinone. The polyamine profile composed of 2-hydroxyputrescine, spermidine, putrescine, and benzoic acid. A genomic DNA G+C content was 51.4 mol%. The average nucleotide identity between strains S11R28(T) and U. parvum DSM 23061(T) was 78.66%. Thus, Undibacterium piscinae can be considered a novel species within the genus Undibacterium with the type strain S11R28(T) (=KCTC 62668(T)=JCM 33224(T)).
ESTHER : Lee_2019_Int.J.Syst.Evol.Microbiol_69_3148
PubMedSearch : Lee_2019_Int.J.Syst.Evol.Microbiol_69_3148
PubMedID: 31385778
Gene_locus related to this paper: 9burk-a0a6m4abh3

Title : Multifunctional Activity of Polyphenolic Compounds Associated with a Potential for Alzheimer's Disease Therapy from Ecklonia cava - Choi_2015_Phytother.Res_29_549
Author(s) : Choi BW , Lee HS , Shin HC , Lee BH
Ref : Phytother Res , 29 :549 , 2015
Abstract : Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 muM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol-A (PFF-A), showed a particularly potent inhibitory activity (IC50 0.95 muM), which is over 100-fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Abeta. Bieckol and PFF-A inhibited amyloid precursor protein biosynthesis. PFF-A also showed very strong beta-secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease. Copyright (c) 2015 John Wiley & Sons, Ltd.
ESTHER : Choi_2015_Phytother.Res_29_549
PubMedSearch : Choi_2015_Phytother.Res_29_549
PubMedID: 25640212

Title : Ice plant (Mesembryanthemum crystallinum) improves hyperglycaemia and memory impairments in a Wistar rat model of streptozotocin-induced diabetes - Lee_2014_J.Sci.Food.Agric_94_2266
Author(s) : Lee BH , Lee CC , Wu SC
Ref : J Sci Food Agric , 94 :2266 , 2014
Abstract : BACKGROUND: Ice plant (Mesembryanthemum crystallinum) has been used as an anti-diabetic agent in Japan because it contains d-pinitol. The efficacy of ice plant in the regulation of blood glucose is unclear at present. Recently, memory impairment and development of Alzheimer's disease found in diabetic patients are thought to be caused by high blood glucose. The mechanism by which ice plant protects against the impairment of memory and learning abilities caused by high blood glucose remains unclear. The aim of this study was to evaluate the protection of ice plant water extracts (IPE) and d-pinitol against memory impairments in a Wistar rat model of streptozotocin (STZ)-induced diabetes. We hypothesised that IPE and d-pinitol could suppress blood glucose and elevate insulin sensitivity in these rats.
RESULTS: For memory evaluation, IPE and d-pinitol also improved the passive avoidance task and the working memory task. In addition, inhibition of acetylcholinesterase activity in hippocampus and cortex was found in this rat model administered IPE or d-pinitol. IPE and d-pinitol also markedly elevated superoxide dismutase activity against oxidative stress and reduced malondialdehyde production in hippocampus and cortex of the rats. CONCLUSION: These findings indicated that IPE and d-pinitol possess beneficial effects for neural protection and memory ability in a rat model of diabetes. (c) 2013 Society of Chemical Industry.
ESTHER : Lee_2014_J.Sci.Food.Agric_94_2266
PubMedSearch : Lee_2014_J.Sci.Food.Agric_94_2266
PubMedID: 24374864

Title : Effects of a new synthetic butyrylcholinesterase inhibitor, HBU-39, on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia animal model - Yoo_2011_Neurochem.Int_59_722
Author(s) : Yoo DY , Woo YJ , Kim W , Nam SM , Lee BH , Yeun GH , Yoon YS , Won MH , Park JH , Hwang IK
Ref : Neurochem Int , 59 :722 , 2011
Abstract : In this study, we synthesized [1-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-5-(1,2-dithiolan-3-yl)penta n-1-one, HBU-39], a (alpha)-lipoic acid derivative, and found this compound strongly inhibited butyrylcholinesterase (BuChE) in an in vitro experiment. We also examined the effects of HBU-39 on cell proliferation and neuroblast differentiation using the specific markers Ki67 and doublecortin (DCX), respectively, in the hippocampal dentate gyrus of a rat model of scopolamine-induced amnesia. For this, scopolamine was subcutaneously administered for 28 days by an ALzet osmotic minipump (44 mg/mL delivered at 2.5 muL/h). HBU-39 (1mg/kg per day) and galantamine (an acetylcholinesterase inhibitor used as a control; 5mg/kg per day) were intraperitoneally administered for 28 days. The administration of scopolamine significantly decreased the mean number of Ki67- and DCX-immunoreactive cells in the dentate gyrus. However, treatment with both HBU-39 and galantamine significantly ameliorated the reductions in cell proliferation and neuroblast differentiation. In particular, the mean number of Ki67- and DCX-immunoreactive cells was prominently abundant in the HBU-treated group compared to that in the galantamine-treated group. These results suggest that the BuChE inhibitor, HBU-39, can ameliorate the scopolamine-induced reductions of cell proliferation and neuroblast differentiation, and HBU-39 may be applicable to amnesia patients to promote memory functions.
ESTHER : Yoo_2011_Neurochem.Int_59_722
PubMedSearch : Yoo_2011_Neurochem.Int_59_722
PubMedID: 21771623

Title : Anticholinesterase activity of plastoquinones from Sargassum sagamianum: lead compounds for Alzheimer's disease therapy - Choi_2007_Phytother.Res_21_423
Author(s) : Choi BW , Ryu G , Park SH , Kim ES , Shin J , Roh SS , Shin HC , Lee BH
Ref : Phytother Res , 21 :423 , 2007
Abstract : During the search for anticholinesterase compounds from marine organisms, two known plastoquinones, sargaquinoic acid (1) and sargachromenol (2), were isolated from Sargassum sagamianum. Both compounds showed moderate acetylcholinesterase (AChE) inhibitory activity in a micromole range (IC(50) 23.2 and 32.7 microm, respectively). However, for butyrylcholinesterase (BuChE), a new target for the treatment of Alzheimer's disease (AD), compound 1 showed particularly potent inhibitory activity (IC(50) 26 nm), which is 1000-fold greater than for AChE. Hence, sargaquinoic acid represents an effective and selective inhibitor of BuChE with a potency similar to or greater than the anticholinesterases in current clinical use, making it an interesting potential drug candidate for AD.
ESTHER : Choi_2007_Phytother.Res_21_423
PubMedSearch : Choi_2007_Phytother.Res_21_423
PubMedID: 17236179

Title : Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model - Wernig_2006_Blood_107_4274
Author(s) : Wernig G , Mercher T , Okabe R , Levine RL , Lee BH , Gilliland DG
Ref : Blood , 107 :4274 , 2006
Abstract : An acquired somatic mutation, Jak2V617F, was recently discovered in most patients with polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), and essential thrombocythemia (ET). To investigate the role of this mutation in vivo, we transplanted bone marrow (BM) transduced with a retrovirus expressing either Jak2 wild-type (wt) or Jak2V617F into lethally irradiated syngeneic recipient mice. Expression of Jak2V617F, but not Jak2wt, resulted in clinicopathologic features that closely resembled PV in humans. These included striking elevation in hemoglobin level/hematocrit, leukocytosis, megakaryocyte hyperplasia, extramedullary hematopoiesis resulting in splenomegaly, and reticulin fibrosis in the bone marrow. Histopathologic and flow cytometric analyses showed an increase in maturing myeloid lineage progenitors, although megakaryocytes showed decreased polyploidization and staining for acetylcholinesterase. In vitro analysis of primary cells showed constitutive activation of Stat5 and cytokine-independent growth of erythroid colony-forming unit (CFU-E) and erythropoietin hypersensitivity, and Southern blot analysis for retroviral integration indicated that the disease was oligoclonal. Furthermore, we observed strain-specific differences in phenotype, with Balb/c mice demonstrating markedly elevated leukocyte counts, splenomegaly, and reticulin fibrosis compared with C57Bl/6 mice. We conclude that Jak2V617F expression in bone marrow progenitors results in a PV-like syndrome with myelofibrosis and that there are strain-specific modifiers that may in part explain phenotypic pleiotropy of Jak2V617F-associated myeloproliferative disease in humans.
ESTHER : Wernig_2006_Blood_107_4274
PubMedSearch : Wernig_2006_Blood_107_4274
PubMedID: 16478879

Title : Improvement of memory by dieckol and phlorofucofuroeckol in ethanol-treated mice: possible involvement of the inhibition of acetylcholinesterase - Myung_2005_Arch.Pharm.Res_28_691
Author(s) : Myung CS , Shin HC , Bao HY , Yeo SJ , Lee BH , Kang JS
Ref : Arch Pharm Res , 28 :691 , 2005
Abstract : Phlorotannins, the polyphonic compounds found in brown Eisenia and Ecklonia algae, have several pharmacologically beneficial effects such as anti-inflammation. In addition, our recent data show that these compounds may improve the cognitive functions of aged humans suggesting the potential ability to enhance memory in several neurodegenerative disorders. To examine the experimental hypothesis that two effective components of Ecklonia cava, dieckol and phlorofucofuroeckol (PFF), have memory-enhancing abilities, both were administered orally to mice before a passive avoidance test. The repeated administration of either dieckol or PFF dose-dependently reduced the inhibition of latency by the administration of ethanol. To investigate the mode of memory-enhancing actions, the levels of major central neurotransmitters in three different regions (striatum, hippocampus, and frontal cortex) of the mouse brain were measured. The levels of some of the neurotransmitters were significantly changed by ethanol. Both dieckol and PFF altered the levels of some neurotransmitters modified by the ethanol treatment. It is noteworthy that both dieckol and PFF increased the level of acetylcholine, and they exerted anticholinesterase activities. Overall, the memory-enhancing abilities of dieckol and PFF may result from, at least in part, the increment of the brain level of acetylcholine by inhibiting acetylcholinesterase.
ESTHER : Myung_2005_Arch.Pharm.Res_28_691
PubMedSearch : Myung_2005_Arch.Pharm.Res_28_691
PubMedID: 16042079

Title : Characterization and heterologous gene expression of a novel esterase from Lactobacillus casei CL96 - Choi_2004_Appl.Environ.Microbiol_70_3213
Author(s) : Choi YJ , Miguez CB , Lee BH
Ref : Applied Environmental Microbiology , 70 :3213 , 2004
Abstract : A novel esterase gene (estI) of Lactobacillus casei CL96 was localized on a 3.3-kb BamHI DNA fragment containing an open reading frame (ORF) of 1,800 bp. The ORF of estI was isolated by PCR and expressed in Escherichia coli, the methylotrophic bacterium Methylobacterium extorquens, and the methylotrophic yeast Pichia pastoris under the control of T7, methanol dehydrogenase (P(mxaF)), and alcohol oxidase (AOX1) promoters, respectively. The amino acid sequence of EstI indicated that the esterase is a novel member of the GHSMG family of lipolytic enzymes and that the enzyme contains a lipase-like catalytic triad, consisting of Ser325, Asp516, and His558. E. coli BL21(DE3)/pLysS containing estI expressed a novel 67.5-kDa protein corresponding to EstI in an N-terminal fusion with the S. tag peptide. The recombinant L. casei CL96 EstI protein was purified to electrophoretic homogeneity in a one-step affinity chromatography procedure on S-protein agarose. The optimum pH and temperature of the purified enzyme were 7.0 and 37 degrees C, respectively. Among the pNP (p-nitrophenyl) esters tested, the most selective substrate was pNP-caprylate (C(8)), with K(m) and k(cat) values of 14 +/- 1.08 microM and 1,245 +/- 42.3 S(-1), respectively.
ESTHER : Choi_2004_Appl.Environ.Microbiol_70_3213
PubMedSearch : Choi_2004_Appl.Environ.Microbiol_70_3213
PubMedID: 15184114
Gene_locus related to this paper: lacca-ESTI

Title : N-nitroso metabolite of carbofuran induces apoptosis in CHL cells by cytochrome c-mediated activation of caspases - Lee_2004_Toxicology_201_51
Author(s) : Lee BW , Oh SH , Chung JH , Moon CK , Lee BH
Ref : Toxicology , 201 :51 , 2004
Abstract : Carbofuran is an anti-acetylcholinesterase insecticide regarded as a relatively safe chemical based on extensive toxicological data. However, the N-nitroso metabolite of carbofuran has been reported to be genotoxic. We previously observed that N-nitrosocarbofuran (NOCF) induces apoptosis and cell cycle arrest in Chinese hamster lung (CHL) fibroblasts. To extend our initial observations, we investigated the molecular mechanism of NOCF-induced apoptosis. Treatment of cells with NOCF caused dose-dependent upregulation of cytosolic factors, such as Bax and Bid, and release of cytochrome c, which were accompanied by activation of caspase-9. We also observed activation of caspase-8 and caspase-3, and subsequent cleavage of poly(ADP-ribose) polymerase. A broad-spectrum caspase inhibitor and a caspase-8-specific inhibitor completely blocked caspase-3 activation and cell death induced by NOCF. These results suggest that the mitochondrial pathway is primarily involved in the NOCF-induced apoptosis of CHL cells.
ESTHER : Lee_2004_Toxicology_201_51
PubMedSearch : Lee_2004_Toxicology_201_51
PubMedID: 15297019

Title : Cholinesterase inhibitory activity of two farnesylacetone derivatives from the brown alga Sargassum sagamianum - Ryu_2003_Arch.Pharm.Res_26_796
Author(s) : Ryu G , Park SH , Kim ES , Choi BW , Ryu SY , Lee BH
Ref : Arch Pharm Res , 26 :796 , 2003
Abstract : Two known farnesylacetone derivatives (1 and 2) were isolated from the Korean brown alga Sargassum sagamianum off Jeju Island, Korea. Compounds 1 and 2 were identified as (5E,10Z)-6,10,14-trimethylpentadeca-5,10-dien-2,12-dione and (5E,9E,13E)-6,10,4-trimethyl-pentadeca-5,9,13-trien-2,12-dione, respectively, by comparison with the literature data. Compounds 1 and 2 showed moderate acetylcholinesterase and butyrylcholinesterase inhibitory activities with IC50 values of 65.0 approximately 48.0 and 34.0 approximately 23.0 microM, respectively.
ESTHER : Ryu_2003_Arch.Pharm.Res_26_796
PubMedSearch : Ryu_2003_Arch.Pharm.Res_26_796
PubMedID: 14609125

Title : N-nitrosocarbofuran induces apoptosis in mouse brain microvascular endothelial cells (bEnd.3) - Jung_2003_J.Pharmacol.Sci_93_489
Author(s) : Jung YS , Kim CS , Park HS , Sohn S , Lee BH , Moon CK , Lee SH , Baik EJ , Moon CH
Ref : J Pharmacol Sci , 93 :489 , 2003
Abstract : In this study, we investigated whether carbofuran, a commonly used carbamate pesticide, and N-nitrosocarbofuran (NOCF), the N-nitroso metabolite of carbofuran, have cytotoxicity in mouse brain microvascular endothelial cells (bEnd.3). Results from the MTT assay in bEnd.3 cells showed that NOCF but not carbofuran caused a remarkable decrease in cell viability. The cell death induced by NOCF appeared to involve apoptosis, based on our results from annexin V staining and electron microscopy. To investigate the mechanism of the NOCF-induced cell death, we examined the effects of selective inhibitors for MAP kinase pathways, PD98059 (for MEK/ERK), SB202190 (for p38 MAP kinase), and SP600125 (for JNK), on the NOCF-induced cell death. The NOCF-induced cell death was significantly reduced by PD98059, but not by SB202190 or SP600125. NOCF increased ERK phosphorylation as early as 15 min after the treatment and this increase was maintained for 2 h. In summary, our results suggest that NOCF can induce apoptotic cell death, at least in part, through the ERK pathway in brain microvascular endothelial cells.
ESTHER : Jung_2003_J.Pharmacol.Sci_93_489
PubMedSearch : Jung_2003_J.Pharmacol.Sci_93_489
PubMedID: 14737022

Title : Fumigant toxicity of volatile natural products from Korean spices and medicinal plants towards the rice weevil, Sitophilus oryzae (L) - Lee_2001_Pest.Manag.Sci_57_548
Author(s) : Lee SE , Lee BH , Choi WS , Park BS , Kim JG , Campbell BC
Ref : Pest Manag Sci , 57 :548 , 2001
Abstract : The fumigant toxicity of various volatile constituents of essential oils extracted from sixteen Korean spices and medicinal plants towards the rice weevil, Sitophilus oryzae L (Coleoptera: Curculionidae), was determined. The most potent toxicity was found in the essential oil from Mentha arvensis L. var piperascens (LC50 = 45.5 microliters litre-1 air). GC-MS analysis of essential oil from M arvensis showed it to be rich in menthol (63.2%), menthone (13.1%) and limonene (1.5%), followed in abundance by beta-pinene (0.7%), alpha-pinene (0.6%) and linalool (0.2%). Treatment of S oryzae with each of these terpenes showed menthone to be most active (LC50 = 12.7 microliters litre-1 air) followed by linalool (LC50 = 39.2 microliters litre-1 air) and alpha-pinene (LC50 = 54.9 microliters litre-1 air). Studies on inhibition of acetylcholinesterase activity of S oryzae showed menthone to have a nine-fold lower inhibitory effect than menthol, despite menthone being 8.1-fold more toxic than menthol to the rice weevil. Different modes of toxicity of these monoterpenes towards S oryzae are discussed.
ESTHER : Lee_2001_Pest.Manag.Sci_57_548
PubMedSearch : Lee_2001_Pest.Manag.Sci_57_548
PubMedID: 11407032

Title : Inhibition of electric eel acetylcholinesterase by porphin compounds - Lee_1998_Bioorg.Med.Chem.Lett_8_1467
Author(s) : Lee BH , Park MB , Yu BS
Ref : Bioorganic & Medicinal Chemistry Lett , 8 :1467 , 1998
Abstract : Synthetic porphin compounds have been found to be reversible inhibitors of acetylcholinesterase from electric eel with Ki values of microM range. It seems that the number and position of fluorine on the phenyl ring and metal of an inhibitor play an important role for binding of an inhibitor to the enzyme active site.
ESTHER : Lee_1998_Bioorg.Med.Chem.Lett_8_1467
PubMedSearch : Lee_1998_Bioorg.Med.Chem.Lett_8_1467
PubMedID: 9873371

Title : Inhibition of acetylcholinesterase by hemicholiniums, conformationally constrained choline analogues. Evaluation of aryl and alkyl substituents. Comparisons with choline and (3- hydroxyphenyl)trimethylammonium - Lee_1992_Chem.Res.Toxicol_5_411
Author(s) : Lee BH , Stelly TC , Colucci WJ , Garcia JG , Gandour RD , Quinn DM
Ref : Chemical Research in Toxicology , 5 :411 , 1992
Abstract : 2-Substituted-2-hydroxy-4,4-dimethylmorpholiniums (hemicholiniums) inhibit acetylcholinesterase (EC 3.1.1.7)-catalyzed hydrolysis of acetylthiocholine (ATCh). The 4-substituted arenes [NH2, NHC(O)CH3, Cl, CN, and NO2] have values of inhibition constants (Ki) that range from 220 to 3690 microM, which correlate with Hammett sigma, rho approximately 0.8. The alkyl compounds, hydrogen, methyl, tert-butyl, and trifluoromethyl, have values of Ki of 550, 560, 1200, and 1200 microM, respectively. These values compare favorably with Ki = 960 microM for choline. The conformation of AChE-bound choline must be gauche to support our suggestion that hemicholiniums are conformationally constrained analogues of choline. (3-Hydroxyphenyl)trimethylammonium (5) inhibits most strongly, Ki = 0.21 microM, of the compounds examined in this study. The solvent isotope effect (H2OKi/D2OKi = 0.83 +/- 0.04) suggests that inhibition by 5 involves hydrogen bonding. The binding by AChE of the hemicholiniums of various sizes and the strong binding of 5 support an earlier proposal [Schowen, K. B., Smissman, E. E., and Stephen, W. F., Jr. (1975) J. Med. Chem. 18, 292-300] that the active site of AChE has ample space for rotation about the C-C bond in choline. Compound 5, which has one more carbon between the hydroxy and trimethylammonium than does choline, inhibits much more potently than either choline or the hemicholiniums. Compound 5 provides a correct spacer to span the trimethylammonium recognition site and the esteratic site of AChE. This aromatic spacer interacts favorably with the hydrophobic active site, and the phenolic hydroxyl probably hydrogen bonds to the histidine in the esteratic site. Choline in any conformation and the hemicholiniums are too short to make a strong hydrogen bond.
ESTHER : Lee_1992_Chem.Res.Toxicol_5_411
PubMedSearch : Lee_1992_Chem.Res.Toxicol_5_411
PubMedID: 1504265

Title : The Chemical Mechanism of Acetylcholinesterase Reactions: Biological Catalysis at the Speed Limit -
Author(s) : Quinn DM , Pryor AN , Selwood T , Lee BH , Acheson SA , Barlow PN
Ref : In: Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology , (Massoulie J, Barnard EA, Chatonnet A, Bacou F, Doctor BP, Quinn DM) American Chemical Society, Washington, DC :252 , 1991
PubMedID: