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1.
Jerzy Mroziński Alina Bieńko Pavel Kopel Vratislav Langer 《Inorganica chimica acta》2008,361(12-13):3723-3729
Novel trinuclear Ni(II) complex [Ni3(pmdien)3(btc)(H2O)3](ClO4)3 · 4H2O, 1 where pmdien = N,N,N′,N′,N″-pentamethyldiethylenetriamine, H3btc = 1,3,5-benzenetricarboxylic (trimesic) acid, has been prepared and structurally characterized. Three nickel atoms are bridged by btc trianion and their coordination sphere is completed by three N atoms of pmdien and O atom of the water molecule. The three nickel(II) magnetic centers are equivalent and their coordination spheres are completed to deformed octahedrons. Magnetic susceptibility was measured over the temperature range 1.8–300 K and zJ′ = ?0.19 cm?1, D = 3.79 cm?1, g = 2.18 parameters were calculated. 相似文献
2.
3.
K.S. Shashidhara Sushama M. Gaikwad 《International journal of biological macromolecules》2009,44(1):112-115
Energetics of the catalysis of Class II α-mannosidase (E.C.3.2.1.24) from Aspergillus fischeri was studied. The enzyme showed Kcat/Km for Man (α1-3) Man, Man (α1-2) Man and Man (α1-6) Man as 7488, 5376 and 3690 M?1 min?1, respectively. The activation energy, Ea was 15.14, 47.43 and 71.21 kJ/mol for α1-3, α1-2 and α1-6 linked mannobioses, respectively, reflecting the energy barrier in the hydrolysis of latter two substrates. The enzyme showed Kcat/Km as 3.56 × 105 and 4.61 × 105 M?1 min?1 and Ea as 38.7 and 8.92 kJ/mol, towards pNPαMan and 4-MeUmbαMan, respectively. Binding of Swainsonine to the enzyme is stronger than that of 1-deoxymannojirimycin. 相似文献
4.
Inga Hoffmann Mats Hamberg Roland Lindh Ernst H. Oliw 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(12):1508-1517
Cyclooxygenases (COX) and 8R-dioxygenase (8R-DOX) activities of linoleate diol synthases (LDS) are homologous heme-dependent enzymes that oxygenate fatty acids by a tyrosyl radical-mediated hydrogen abstraction and antarafacial insertion of O2. Soybean lipoxygenase-1 (sLOX-1) contains non-heme iron and oxidizes 18:2n ? 6 with a large deuterium kinetic isotope effect (D-KIE). The aim of the present work was to obtain further mechanistic insight into the action of these enzymes by using a series of n ? 6 and n ? 9 fatty acids and by analysis of D-KIE. COX-1 oxidized C20 and C18 fatty acids in the following order of rates: 20:2n ? 6 > 20:1n ? 6 > 20:3n ? 9 > 20:1n ? 9 and 18:3n ? 3 ≥ 18:2n ? 6 > 18:1n ? 6. 18:2n ? 6 and its geometrical isomer (9E,12Z)18:2 were both mainly oxygenated at C-9 by COX-1, but the 9Z,12E isomer was mostly oxygenated at C-13. A cis-configured double bond in the n ? 6 position therefore seems important for substrate positioning. 8R-DOX oxidized (9Z,12E)18:2 at C-8 in analogy with 18:2n ? 6, but the 9E,12Z isomer was mainly subject to hydrogen abstraction at C-11 and oxygen insertion at C-9 by 8R-DOX of 5,8-LDS. sLOX-1 and 13R-MnLOX oxidized [11S-2H]18:2n ? 6 with similar D-KIE (~ 53), which implies that the catalytic metals did not alter the D-KIE. Oxygenation of 18:2n ? 6 by COX-1 and COX-2 took place with a D-KIE of 3–5 as probed by incubations of [11,11-2H2]- and [11S-2H]18:2n ? 6. In contrast, the more energetically demanding hydrogen abstractions of the allylic carbons of 20:1n ? 6 by COX-1 and 18:1n ? 9 by 8R-DOX were both accompanied by large D-KIE (> 20). 相似文献
5.
In vitro studies suggested that nitrite may play a cytoprotective role in inflammation. The aim of the present clinical study was to investigate the relationship between the NO metabolites nitrite and nitrate and the biomarkers of oxidative stress 3-nitrotyrosine (3-NT) and 15(S)-iso-PGF2α in patients suffering from chronic inflammatory rheumatic diseases. In morning urine from 28 patients with different chronic inflammatory rheumatic diseases (23–82 years of age) and from 41 healthy persons of both genders, nitrite and nitrate were quantitated by GC-MS, and 3-NT and 15(S)-iso-PGF2α by GC-MS/MS. Mean creatinine-corrected urinary excretion rates of nitrite (1.1 versus 0.19 μmol/mmol, P = 0.00012) and 3-NT (1.2 versus 0.39 nmol/mmol, P = 0.01629), but not of nitrate (105 versus 106 μmol/mmol), were significantly elevated in rheumatism as compared to health. Urinary excretion rate of 15(S)-iso-PGF2α did not differ between patients and healthy subjects (65 versus 69 pmol/mmol creatinine, P = 0.48). In rheumatism, urinary 3-NT correlated closely with nitrite (R = 0.788, P < 0.0001) and moderately with nitrate (R = 0.45, P < 0.016), but did not correlate with 15(S)-iso-PGF2α (R = ?0.083, P = 0.68). In healthy persons there was no correlation between urinary 3-NT and nitrite or nitrate. Our study suggests that urinary nitrite may represent a novel specific biomarker of nitrative stress in chronic inflammatory rheumatic disease. In another eight patients with chronic inflammatory rheumatic diseases we found higher nitrite concentrations in synovial fluid as compared to serum (1.30 versus 0.35 μM). We hypothesize that in chronic inflammatory rheumatic diseases nitrite concentration is elevated in the inflamed joint and contributes to the inactivation of myeloperoxidase-catalyzed production of hypochloric acid by forming nitryl chloride which eventually nitrates tyrosine to form 3-NT. 相似文献
6.
Two tetracyanometalate building blocks, [Fe(5,5′-dmbipy)(CN)4]? (2) and [Fe(4,4′-dmbipy)(CN)4]? (3) (5,5′-dmbipy = 5,5′-dimethyl-2,2′-bipyridine; 4,4′-dmbipy = 4,4′-dimethyl-2,2′-bipyridine), and two cyano-bridged heterobimetallic complexes, [Cu2(bpca)2(H2O)2Fe2(5,5′-dmbipy)2(CN)8] · 2[Cu(bpca)Fe(5,5′-dmbipy)(CN)4] · 4H2O (4) and [Cu(bpca)Fe(4,4′-dmbipy)(CN)4]n (5) (bpca = bis(2-pyridylcarbonyl)amidate), have been synthesized and structurally characterized. Complex 4 contains two dinuclear and one tetranuclear heterobimetallic clusters in an asymmetric unit whereas the structure of complex 5 features a one-dimensional heterobimetallic zigzag chain. The Cu(II) ion is penta-coordinated in the form of a distorted square-based pyramid. Magnetic studies show ferromagnetic coupling between Cu(II) and Fe(III) ions with g = 2.28, J1 = 2.64 cm?1, J2 = 5.40 cm?1 and TIP = ?2.36 × 10?3 for complex 4, and g = 2.17, J = 4.82 cm?1 and zJ′ = 0.029 cm?1 for complex 5. 相似文献
7.
《Inorganica chimica acta》2006,359(6):1855-1869
A series of discrete, mononuclear palladium(II)–methyl complexes, together with several palladium(II)–chloro analogues, of pyridine-functionalised bis-NHC ligands have been prepared via ligand transmetallation from the silver(I)-NHC complexes. The reported complexes comprise examples with both the methylene-bridged 2,6-bis[(3-R-imidazolin-2-yliden-1-yl)methyl]pyridine (RC∧N∧C; R = Mes, dipp, tBu) and planar 2,6-bis(3-R-imidazolin-2-yliden-1-yl)pyridine (RCNC; R = Mes, dipp) ligands and, when combined with the previously reported MeC∧N∧C/MeCNC examples, cover a broad spectrum of ligand substituent steric and electronic properties, including the bulky Mes and dipp groups frequently used in catalytic applications. The palladium(II) complexes have been characterised by a variety of methods, including single crystal X-ray crystallography, with the shielding of the Pd–Me groups in the proton NMR spectra of some of the N-aryl substituted examples correlated with the proximity of the aryl rings to the methyl group in the solid state structures. The [PdMe(RC∧N∧C/RCNC)]+ complexes undergo thermal degradation via reductive methyl-NHC coupling to give 2-methyl-3-R-imidazolium-1-yl species with relative stabilities in the order of [PdMe(MesC∧N∧C)]BF4 > [PdMe(MeC∧N∧C)]BF4 ≈ [PdMe(MesCNC)]BF4 > [PdMe(MeCNC)]BF4 > [PdMe(tBuC∧N∧C)]BF4 ≫ [PdMe(tBuCNC)]BF4 (not isolable). A comparison of the activity of the complexes as precatalysts in a model Heck coupling reaction shows greatest activity in those species bearing bulkier N-substituents, with complexes bearing RC∧N∧C ligands generally more efficient precatalysts than those bearing RCNC ligands. 相似文献
8.
Ana Isabel Martínez-Gómez Josefa María Clemente-Jiménez Felipe Rodríguez-Vico Liisa T. Kanerva Xiang-Guo Li Francisco Javier Las Heras-Vázquez Sergio Martínez-Rodríguez 《Process Biochemistry》2012,47(12):2090-2096
Taking advantage of the catalytic promiscuity of pyrimidine-catabolism enzymes (dihydropyrimidinase (E.C. 3.5.2.2), N-carbamoyl-β-alanine amidohydrolase (E.C. 3.5.1.6)), the production of different β-alanine derivatives starting from 5- and 6-monosubstituted dihydrouracils has been evaluated using a mimesis approach. In this work, the S-enantioselective character of dihydropyrimidinase from Sinorizhobium meliloti toward 6-monosubstituted dihydrouracil derivatives has been shown. An inverted R-/S-enantioselectivity of N-carbamoyl-β-alanine amidohydrolase from Agrobacterium tumefaciens toward two different N-carbamoyl-β-amino acids has been proved. Our results have shown for the first time that this mimetic tandem constitutes an interesting biotechnological tool for the preparation of different β-alanine derivatives in an environmentally friendly way, allowing the production of enantioenriched (R)-α-phenyl-β-alanine (e.e. > 95%) and (R)-α-methyl-β-alanine (e.e. > 90%). 相似文献
9.
Robert T. Butcher Christopher P. Landee Mark M. Turnbull Fan Xiao 《Inorganica chimica acta》2008,361(12-13):3654-3658
The structure of copper pyrazine dibromide (or dichloride) consists of dihalide-bridged copper chains parallel to the c-axis with the copper sites linked in a perpendicular direction by bridging pyrazine molecules parallel to the b-axis. Superexchange interactions are propagated through both halides and pyrazine so the magnetic structure is a rectangular layer with two exchange strengths, J and J′ (J′ = αJ), where 0 < α < 1. The susceptibility of a rectangular antiferromagnetic Heisenberg lattice with S = 1/2 has been simulated using Quantum Monte Carlo techniques and the results compared to the experimental data. Best fits of the magnetic susceptibility data to the simulated data yield: for Cu(pz)Br2, α = 0.20(5), C = 0.430(1) emu K/mol, 2J = ?46(1) K, and 2J′ = ?9(2) K and for Cu(pz)Cl2, α = 0.30(5), C = 0.426(1) emu K/mol, 2J = ?28(1) K, and 2J′ = ?8(2)) K. The values are in good agreement with the literature and thus demonstrate the effectiveness of the technique for rectangular lattices. 相似文献
10.
Yin-Lin Zhang Jian-Min Xiao Ji-Li Feng Ke-Wu Yang Lei Feng Li-Sheng Zhou Michael W. Crowder 《Bioorganic & medicinal chemistry letters》2013,23(6):1676-1679
In an effort to prepare a fluorogenic substrate to be used in activity assays with metallo-β-lactamases, (6R,7R)-8-oxo-7-(2-oxo-2H-chromene-3-carboxamido)-3-((4-(2-oxo-2H-chromene-3-carboxamido)-phenylthio)methyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (CA) was synthesized and characterized. CA exhibited a fluorescence quantum yield (φ) of 0.0059, two fluorescence lifetimes of 3.63 × 10?10 and 5.38 × 10?9 s, and fluorescence intensity that is concentration-dependent. Steady-state kinetic assays revealed that CA is a substrate for metallo-β-lactamases (MβLs) L1 and CcrA, exhibiting Km and kcat values of 18 μM and 5 s?1 and 11 μM and 17 s?1, respectively. 相似文献
11.
Denitrifying bioreactors are currently being tested as an option for treating nitrate (NO3?) contamination in groundwater and surface waters. However, a possible side effect of this technology is the production of greenhouse gases (GHG) including nitrous oxide (N2O) and methane (CH4). This study examines NO3? removal and GHG production in a stream-bed denitrifying bioreactor currently operating in Southern Ontario, Canada. The reactor contains organic carbon material (pine woodchips) intended to promote denitrification. Over a 1 year period, monthly averaged removal of influent (stream water) NO3? ranged from 18 to 100% (0.3–2.5 mg N L?1). Concomitantly, reactor dissolved N2O and CH4 production, averaged 6.4 μg N L?1 (2.4 mg N m?2 d?1), and 974 μg C L?1 (297 mg C m?2 d?1) respectively, where production is calculated as the difference between inflow and effluent concentrations. Gas bubbles entrapped in sediments overlying the reactor had a composition ranging from 19 to 64% CH4, 1 to 6% CO2, and 0.5 to 2 ppmv N2O; however, gas bubble emission rates were not quantified in this study. Dissolved N2O production rates from the bioreactor were similar to emission rates reported for some agricultural croplands (e.g. 0.1–15 mg N m?2 d?1) and remained less than the highest rates observed in some N-polluted streams and rivers (e.g. 110 mg N m?2 d?1, Grand R., ON). Dissolved N2O production represented only a small fraction (0.6%) of the observed NO3? removal over the monitoring period. Dissolved CH4 production during summer months (up to 1236 mg C m?2 d?1), was higher than reported for some rivers and reservoirs (e.g. 6–66 mg C m?2 d?1) but remained lower than rates reported for some wastewater treatment facilities (e.g. sewage treatment plants and constructed wetlands, 19,500–38,000 mg C m?2 d?1). 相似文献
12.
S. Kaleem Ahmed Yamina Belabassi Lakshmi Sankaranarayanan Chih-Kai Chao John M. Gerdes Charles M. Thompson 《Bioorganic & medicinal chemistry letters》2013,23(7):2048-2051
Activated organophosphate (OP) insecticides and chemical agents inhibit acetylcholinesterase (AChE) to form OP-AChE adducts. Whereas the structure of the OP correlates with the rate of inhibition, the structure of the OP-AChE adduct influences the rate at which post-inhibitory reactivation or aging phenomena occurs. In this report, we prepared a panel of β-substituted ethoxy and γ-substituted propoxy phosphonoesters of the type p-NO2PhO-P(X)(R)[(O(CH2)nZ] (R = Me, Et; X = O, S; n = 2, 3; Z = halogen, OTs) and examined the inhibition of three AChEs by select structures in the panel. The β-fluoroethoxy methylphosphonate analog (R = Me, Z = F, n = 2) was the most potent anti-AChE compound comparable (ki ~6 × 106 M?1 min?1) to paraoxon against EEAChE. Analogs with Z = Br, I, or OTs were weak inhibitors of the AChEs, and methyl phosphonates (R = Me) were more potent than the corresponding ethyl phosphonates (R = Et). As expected, analogs with a thionate linkage (PS) were poor inhibitors of the AChEs. 相似文献
13.
Magdalena Korecka Christopher M. Clark Virginia M.-Y. Lee John Q. Trojanowski Leslie M. Shaw 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(24):2209-2216
Quantitation of isoprostanes such as 8-iso-PGF2α and 8,12-iso-iPF2α-VI in biological fluids has been proposed as a reliable test of oxidant stress and inflammation in a variety of disorders. This paper presents a liquid chromatography method with tandem mass spectrometry detection for the simultaneous analysis of these two isoprostanes in human CSF and brain tissue samples. An API 5000 triple quadrupole instrument (AB Sciex, Foster City, CA, USA) with an APCI ion source was used in this study. Aliquots of CSF samples (0.25 mL) were treated with a methanol:zinc sulfate mixture followed by on-line cleanup on an extraction column (Validated-C18) with 0.1% formic acid. The brain tissue samples were homogenized and lipids were extracted using Folch solution. Solid-phase extraction columns (C18) were used for the purification of the brain isoprostane fraction. Chromatographic separation was achieved using an analytical column (Synergi C18 HydroRP) with 0.1% formic acid in water and a mixture of methanol:acetonitrile under isocratic conditions. The mass spectrometer was operated in the MRM scan and negative ion mode. The quadrupoles were set to detect the molecular ions [M?H]? and high mass fragments of isoprostanes: m/z 353 → 193 amu (8-iso-PGF2α) and m/z 353 → 115 amu (8,12-iso-iPF2α-VI) and their deuterated internal standards: m/z 357 → 197 amu (8-iso-PGF2α-d4) and m/z 364 → 115 amu (8,12-iso-iPF2α-VI-d11). The lower limit of quantification was 2.5 pg/mL for 8-iso-PGF2α and 5.0 pg/mL for 8,12-iso-PF2α-VI for the CSF method and 10.0 pg/0.1 g of tissue and 30.0 pg/0.1 g of tissue for 8-iso-PGF2α and 8,12-iso-iPF2α-VI, respectively, for the brain tissue method. No ion suppression or enhancement of the detection of 8-isoPGF2α, 8,12-isoPF2α-VI or both internal standards was found. 相似文献
14.
《Inorganica chimica acta》2006,359(4):1114-1120
A series of new hexa-coordinated ruthenium(III) complexes of the type [RuX(Nap-o-phd)(EPh3)] (where, H2-Nap-o-phd = N,N′-bis(2-hydroxy-1-naphthaldehyde) o-phenylene diamine; X = Cl or Br; E = P or As) have been prepared by reacting [RuX3(EPh3)3] and [RuBr3(PPh3)2(MeOH)] (where X = Cl or Br; E = P or As) with tetradentate Schiff base ligand (H2-Nap-o-phd) in 1:1 molar ratio. The complexes have been characterized by elemental analyses, infra red, electronic, electron paramagnetic resonance spectroscopy and cyclic voltammetry. The coordination geometry and structure of the complexes have been investigated by extended X-ray absorption fine structure (EXAFS) spectroscopy and an octahedral structure has been proposed. 相似文献
15.
Richard V. Macri Janka Karlovská Gustavo F. Doncel Xiaosong Du Bhadreshkumar B. Maisuria André A. Williams Eko W. Sugandhi Joseph O. Falkinham Alan R. Esker Richard D. Gandour 《Bioorganic & medicinal chemistry》2009,17(8):3162-3168
Three series of homologous dendritic amphiphiles—RCONHC(CH2CH2COOH)3, 1(n); ROCONHC(CH2CH2COOH)3, 2(n); RNHCONHC(CH2CH2COOH)3, 3(n), where R = n-CnH2n+1 and n = 13–22 carbon atoms—were assayed for their potential to serve as antimicrobial components in a topical vaginal formulation. Comparing epithelial cytotoxicities to the ability of these homologues to inhibit HIV, Neisseria gonorrhoeae, and Candida albicans provided a measure of their prophylactic/therapeutic potential. Measurements of the ability to inhibit Lactobacillus plantarum, a beneficial bacterium in the vagina, and critical micelle concentrations (CMCs), an indicator of the potential detergency of these amphiphiles, provided additional assessments of safety. Several amphiphiles from each homologous series had modest anti-HIV activity (EC50 = 110–130 μM). Amphiphile 2(18) had the best anti-Neisseria activity (MIC = 65 μM), while 1(19) and 1(21) had MICs against C. albicans of 16 and 7.7 μM, respectively. Two measures of safety showed promise as all compounds had relatively low cytotoxic activity (EC50 = 210–940 μM) against epithelial cells and low activity against L. plantarum, 1(n), 2(n), and 3(n) had MICs ? 490, 1300, and 940 μM, respectively. CMCs measured in aqueous triethanolamine and in aqueous potassium hydroxide showed linear dependences on chain length. As expected, the longest chain in each series had the lowest CMC—in triethanolamine: 1(21), 1500 μM; 2(22), 320 μM; 3(22), 340 μM, and in potassium hydroxide: 1(21), 130 μM; 3(22), 40 μM. The CMC in triethanolamine adjusted to pH 7.4 was 400 μM for 1(21) and 3900 μM for 3(16). The promising antifungal activity, low activity against L. plantarum, relatively high CMCs, and modest epithelial cytotoxicity in addition to their anti-Neisseria properties warrant further design studies with dendritic amphiphiles to improve their safety indices to produce suitable candidates for antimicrobial vaginal products. 相似文献
16.
《Phytochemistry letters》2008,1(2):89-93
From the leaves of Nelumbo nucifera (an aquatic plant), one new compound, 24(R)-ethylcholest-6-ene-5α-ol-3-O-β-d-glucopyranoside (1), along with 11 known metabolites (2–12), were isolated and identified by spectroscopic methods including 1D- and 2D NMR. Antifungal activity for (R)-roemerine (3) (IC50/MIC = 4.5/10 μg/mL against Candida albicans) and antimalarial activity for (R)-roemerine (3) and N-methylasimilobine (5) (IC50 = 0.2 and 4.8 μg/mL for the D6 clone, respectively, and 0.4 and 4.8 μg/mL for the W2 clone, respectively) was observed. None of the compounds were cytotoxic to Vero cells up to a concentration of 23.8 μg/mL. NMR data for 10-eicosanol (7) and 7,11,15-trimethyl-2-hexadecanone (10) are presented for the first time. An analysis of the structure–activity relationship shows that the substituents in position C-1 and C-2 of aporphine alkaloids are crucial for the antimalarial activity. 相似文献
17.
《生物化学与生物物理学报:生物膜》2015,1848(5):1127-1138
N,N-dimethyldodecylamine-N-oxide (C12NO) is a surfactant that may exist either in a neutral or cationic protonated form depending on the pH of aqueous solutions. Using small angle X-ray diffraction (SAXD) we observe the rich structural polymorphism of pH responsive complexes prepared due to DNA interaction with C12NO/dioleoylphosphatidylethanolamine (DOPE) vesicles and discuss it in view of utilizing the surfactant for the gene delivery vector of a pH sensitive system. In neutral solutions, the DNA uptake is low, and a lamellar Lα phase formed by C12NO/DOPE is prevailing in the complexes at 0.2 ≤ C12NO/DOPE < 0.6 mol/mol. A maximum of ~ 30% of the total DNA volume in the sample is bound in a condensed lamellar phase LαC at C12NO/DOPE = 1 mol/mol and pH 7.2. In acidic conditions, a condensed inverted hexagonal phase HIIC was observed at C12NO/DOPE = 0.2 mol/mol. Commensurate lattice parameters, aHC ≈ dLC, were detected at 0.3 ≤ C12NO/DOPE ≤ 0.4 mol/mol and pH = 4.9–6.4 suggesting that LαC and HIIC phases were epitaxially related. While at the same composition but pH ~ 7, the mixture forms a cubic phase (Pn3m) when the complexes were heated to 80 °C and cooled down to 20 °C. Finally, a large portion of the surfactant (C12NO/DOPE > 0.5) stabilizes the LαC phase in C12NO/DOPE/DNA complexes and the distance between DNA strands (dDNA) is modulated by the pH value. Both the composition and pH affect the DNA binding in the complexes reaching up to ~ 95% of the DNA total amount at acidic conditions. 相似文献
18.
Joaquín Pozo-Dengra Ana Isabel Martínez-Gómez Sergio Martínez-Rodríguez Josefa María Clemente-Jiménez Felipe Rodríguez-Vico Francisco Javier Las Heras-Vázquez 《Process Biochemistry》2009,44(8):835-841
N-Succinylamino acid racemase (NSAAR) with N-acylamino acid racemase (NAAAR) activity together with a d- or l-aminoacylase allows the total transformation of N-acetylamino acid racemic mixtures into optically pure d- or l-amino acids, respectively. In this work we have cloned and expressed the N-succinylamino acid racemase gene from the thermophilic Bacillus-related species Geobacillus kaustophilus CECT4264 in Escherichia coli BL21 (DE3). G. kaustophilus NSAAR (GkNSAAR) was purified in a one-step procedure by immobilized cobalt affinity chromatography and showed an apparent molecular mass of 43 kDa in SDS-gel electrophoresis. Size exclusion chromatography analysis determined a molecular mass of about 150 kDa, suggesting that the native enzyme is a homotetramer. Optimum reaction conditions for the purified enzyme were 55 °C and pH 8.0, using N-acetyl-d-methionine as substrate. GkNSAAR showed a gradual loss of activity at preincubation temperatures over 60 °C, suggesting that it is thermostable. As activity was greatly enhanced by Co2+, Mn2+ and Ni2+ but inhibited by metal-chelating agents, it is considered a metalloenzyme. The Co2+-dependent activity profile of the enzyme was studied with no detectable inhibition at higher metal ion concentrations. GkNSAAR showed activity towards both aliphatic and aromatic N-acetylamino acids such as N-acetyl-methionine and N-acetyl-phenylalanine, respectively, with kcat/Km values ranging from 1 × 103 to 9 × 103 s?1 M?1. Kinetic parameters were better for N-acetyl-d-amino acids than for N-acetyl-l-specific ones. 相似文献
19.
Alexandre V. Ivachtchenko Eugen B. Frolov Oleg D. Mitkin Sergei E. Tkachenko Ilya M. Okun Alex V. Khvat 《Bioorganic & medicinal chemistry letters》2010,20(1):78-82
Syntheses, biological evaluation, and structure–activity relationships for a series of novel 5-styryl and 5-phenethyl analogs of dimebolin are disclosed. The novel derivatives and dimebolin share a broad spectrum of activities against therapeutically relevant targets. Among all synthesized derivatives, 2,8-dimethyl-5-[(Z)-2-phenylvinyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and its 5-phenethyl analog are the most potent blockers of 5-HT7, 5-HT6, 5-HT2C, Adrenergic α2 and H1 receptors. The general affinity rank order towards the studied receptors was Z-3(2) > 4(2) ? 4(3) ? dimebolin, all of them having highest affinities to 5-HT7 receptors. 相似文献
20.
Nikhil Reddy Madadi Narsimha Reddy Penthala Lisa K. Brents Benjamin M. Ford Paul L. Prather Peter A. Crooks 《Bioorganic & medicinal chemistry letters》2013,23(7):2019-2021
A small library of N-benzyl indolequinuclidinone (IQD) analogs has been identified as a novel class of cannabinoid ligands. The affinity and selectivity of these IQDs for the two established cannabinoid receptor subtypes, CB1 and CB2, was evaluated. Compounds 8 (R = R2 = H, R1 = F) and 13 (R = COOCH3, R1 = R2 = H) exhibited high affinity for CB2 receptors with Ki values of 1.33 and 2.50 nM, respectively, and had lower affinities for the CB1 receptor (Ki values of 9.23 and 85.7 nM, respectively). Compound 13 had the highest selectivity of all the compounds examined, and represents a potent cannabinoid ligand with 34-times greater selectivity for CB2R over CB1R. These findings are significant for future drug development, given recent reports demonstrating beneficial use of cannabinoid ligands in a wide variety of human disease states including drug abuse, depression, schizophrenia, inflammation, chronic pain, obesity, osteoporosis and cancer. 相似文献