蛋氨酸亚砜/蛋氨酸亚砜还原酶荧光检测研究进展

蛋白质蛋氨酸亚砜化是一种重要的氧化还原依赖的蛋白质翻译后修饰,不仅是氧化应激的重要标志物之一,也是一种蛋白质功能调控开关可影响活性氧信号转导,与一系列疾病尤其是神经退行性疾病的发生发展密切相关。 在许多生物体中,蛋氨酸亚砜还原酶是目前已经发现的唯一能将蛋白质蛋氨酸亚砜还原为蛋氨酸的物质,可以修复氧化损伤蛋白,恢复蛋白质功能,调控细胞氧还平衡,对相关疾病的治疗具有非常重要的意义。 本文重点介绍蛋氨酸亚砜和蛋氨酸亚砜还原酶的结构和催化机理,综述蛋氨酸亚砜和蛋氨酸亚砜还原酶荧光探针的部分研究进展,对该领域的研究前景进行展望。     

Enantioselective Synthesis of Phenyl-ethanolamines Through Application of Chiral Sulfoxide

Efficient enantioselective synthesis of (R)- and (S)-enantiomers of 2-(tert-butylamino)-1-(p-methoxyphenyl)-ethanol has been achieved in high enantiomeric excess by using asymmetric sulfoxide as a chiral auxiliary. The present synthetic approach was further extended to the asymmetric synthesis of (R)-salbutamol.     

Thallium-205 NMR spectroscopy. Solvation of the Tl(l) ion in the binary solvent systems water/pyridine,water/dimethyl sulfoxide,and pyridine/dimethyl sulfoxide

Solvation of the Tl⁺ ion in 0.005M solutions of water/pyridine, water/dimethyl sulfoxide, and pyridine/dimethyl sulfoxide was studied with ²⁰⁵ Tl NMR spectroscopy as a function of solvent composition and anion (NO ₃ ^– and ClO ₄ ^t- ). Dimethyl sulfoxide solvated the Tl⁺ ion more strongly than did pyridine, despite the latter's greater electron-donating ability. This was explained in terms of structural effects, which were found to be large for all three binary solvent systems. Ion pairing was evident in the DMSO/pyridine and water/pyridine solvent systems in which the pyridine mole fraction was greater than 0.8.     

Thermodynamic Investigation of Dimethyl Sulfoxide Binary Mixtures at 293.15 and 313.15 K

Densities (ρ), speeds of sound (u), and isentropic compressibilities (k _S) of binary mixtures of dimethyl sulfoxide (DMSO) with water, methanol, ethanol, 1-propanol, 2-propanol, acetone and cyclohexanone have been measured over the entire composition range at 293.15 and 313.15 K. The excess molar volumes (V ^E), the deviations in speed of sound (u ^E) and the deviations in isentropic compressibility (k _S ^E) have been determined. The V ^E, u ^E and k _S ^E values were fitted by the Redlich-Kister polynomial equation and the A _k coefficients as well as the standard deviations (d) between the calculated and experimental values have been derived. The results obtained are discussed from the viewpoint of the existence of interactions between the components of the binary mixtures.     

Anthraquinone Electroreduction Mechanism in 0.1 M Tetrabutylammonium Bromide in Dimethyl Sulfoxide

Electroreduction of anthraquinone in 0.1 M tetrabutylammonium bromide in dimethyl sulfoxide is studied by cyclic voltammetry in an argon atmosphere at 373–423 K. According to steady- and non-steady-state measurements, the process involves two one-electron stages at potentials of –0.6 to –0.7 and –1.5 to –1.6 V vs. a quasi-reversible platinum electrode. The electrode material (platinum, silver, glassy carbon) barely affects the electroreduction mechanism. The process is controlled by the mass transfer rate. Anthraquinone can be reduced to mono- and diphenoxide anions. Optimum conditions for obtaining the latter are found.     

Volumetric Properties of the Binary Systems of Dimethyl Sulfoxide with Methacrylic Acid,Vinyl Acetate,Butyl Methacrylate,and Allyl Methacrylate at 298.15 K

Densities of the binary systems of dimethyl sulfoxide with methacrylic acid, vinyl acetate, butyl methacrylate, and allyl methacrylate have been measured as a function of the composition, at 298.15 K and atmospheric pressure, using an Anton Paar DMA 5000 oscillating U-tube densimeter. The calculated excess molar volumes were correlated with the Redlich–Kister equation and with a series of Legendre polynomials. The excess molar volumes are negative for the four binary systems, probably as a result of the large dipole moment of the solvent, and become smaller as the monomer becomes more branched or longer. Methacrylic acid exhibits substantially larger negative excess molar volumes, probably due to hydrogen bonding with the solvent. The system dimethyl sulfoxide with butyl methacrylate presents near ideal behavior.     

亚砜类化合物的合成及应用进展

亚砜类化合物作为一种重要的中间体备受关注,学者们一直努力寻找合适的合成方法.综述了亚砜类化合物的合成方法及应用方面的研究进展,并对发展趋势和应用前景做了展望.     

Density, Excess Volumes, and Partial Volumes of the Binary Systems of Dimethyl Sulfoxide + Ethyl Acrylate, Butyl Acrylate, Methyl Methacrylate, and Styrene at 298.15 K

Densities of the binary systems of dimethyl sulfoxide with ethyl acrylate, butyl acrylate, methyl methacrylate, and styrene have been measured as a function of the composition at 298.15 K and atmospheric pressure using an Anton Paar DMA 5000 oscillating U-tube densimeter. The calculated excess volumes were correlated with the Redlich–Kister equation and with a series of Legendre polynomials. The excess volumes are negative for the four binaries, probably as a result of the large dipole moment of DMSO, becoming smaller as the monomer becomes more branched or longer, and the dipole moment per monomer unit becomes larger.     

青霉素G亚砜对-甲氧基苄基酯的制备

青霉素亚砜;合成;青霉素G亚砜对-甲氧基苄基酯的制备     

二甲基亚砜防冻机理的拉曼光谱分析

采用拉曼光谱对不同体积比的二甲基亚砜(DMSO)水溶液进行测量, 并利用Origin 7.5对水的光谱带进行分峰, 求得拉曼光谱峰面积比值. 应用混合模型对实验结果进行了分析, 分析结果表明, 防冻剂二甲基亚砜与水混合时, 其SO基团与水分子的OH基团形成氢键(SO…H—O), 有效地阻止了四面体结构冰的生成, 并证实了二甲基亚砜与水的体积比为1∶1时, 防冻效果最佳.     

Development of a liquid chromatography/tandem-mass spectrometry assay for the simultaneous determination of teneligliptin and its active metabolite teneligliptin sulfoxide in human plasma

Teneligliptin is a recently developed dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes mellitus. To study simultaneous pharmacokinetics of teneligliptin and its major active metabolite, teneligliptin sulfoxide in human plasma, we developed and validated a LC-MS/MS method. The analytes were detected in the positive mode using multiple reaction monitoring (teneligliptin: m/z 427.2→243.1; teneligliptin-d₈: m/z 435.2→251.3; teneligliptin sulfoxide: m/z 443.2→68.2). The method demonstrated accuracy, precision, and linearity over the concentration range of 5 to 1000 ng/mL for teneligliptin and 2.5 to 500 ng/mL for teneligliptin sulfoxide. The developed method is the first fully validated method capable of simultaneous determination of teneligliptin and its active metabolite, teneligliptin sulfoxide in plasma. The suitability of the method was successfully demonstrated in terms of quantification of teneligliptin and teneligliptin sulfoxide pharmacokinetics in plasma samples collected from healthy volunteers. The measurement of plasma metabolite/parent ratio of teneligliptin was feasible by this method.     

苯基乙酰甲基亚砜与碱土金属配合物的合成和晶体结构(英)

本文选取苯基乙酰甲基亚砜(C₆H₅SOCH₂COCH₃)作为配体与碱土金属(钙、锶)的高氯酸盐反应得到配合物的单晶，对它们进行了元素分析及红外光谱表征，它们的化学式为[ML₆](ClO₄)₂(M=Ca、Sr；L=C₆H₅SOCH₂COCH₃)。并用X-ray单晶衍射法测定了钙、锶配合物的晶体结构。     

Effect of Dimethyl Sulfoxide on the Lamellar Phase of a Zwitterionic Surfactant

We study the effect of dimethyl sulfoxide, a solvent used in biological applications, on the lamellar phases of a zwitterionic surfactant. We used solutions with different proportions of dimethyl sulfoxide/water as solvents in order to analyze the effect on the lamellar phases (regular stacks of surfactant bilayers). The samples were analyzed by macroscopic visual observation, polarized light microscopy, linear rheology, and electron microscopy experiments. The results show that the variation of the dimethyl sulfoxide proportion in the solvent increases the curvature of the bilayers which leads to a transformation from a lamellar phase to an isotropic phase.     

Measurement and Prediction on the Surface Properties of Dimethyl Sulfoxide/Water Mixtures

Pendent drop method was adopted to measure the surface tension of dimethyl sulfoxide(DMSO)/water mixtures. A new pendent drop apparatus was built up and checked with water, and a good agreement of our data with literature could be found. With the new apparatus, the surface tensions of nine DMSO/water mixtures with mass fractions of water from 0.1 to 0.9 were investigated in a temperature range of 298-338 K. The expanded uncertainty for surface tension measurement was estimated to be 0.5% at a confidence level of 95%(k=2) in the whole temperature range. A thermodynamic-based relation was used to predict the surface properties of DMSO/water mixtures. Based on the relation and Gibbs adsorption theory, a prediction model was proposed for the calculation of surface relative excess and the thickness of the surface molecule layer.     

手性苄基甲基亚砜的氯过氧化物酶催化定向合成

基于氯过氧化物酶(CPO)对有机底物的手性识别功能,以CPO催化、叔丁基过氧化氢(TBHP)氧化甲基苄基硫醚合成手性R-苄基甲基亚砜,并在反应体系中引入多羟基化合物及季铵盐提高了目标产物的产率;反应主要受体系的pH值、氧化剂类型、反应时间、氧化剂/底物摩尔比,以及CPO用量等因素控制.引入多羟基化合物(甘油,PEG400,PEG600)时,R-苄基甲基亚砜的产率及ee值可分别达到65.5%和96.3%;而引入季铵盐(TEABr,TPABr,TBABr)时,其产率提高到78.2%～68.5%,ee值为95.4%～94%.UV-vis及荧光光谱分析表明反应体系中引入少量添加剂时CPO活性中心的血红素辅基暴露程度增加,底物容易接近,同时CPO的α-螺旋结构得以加强,从而有效改善了CPO的催化性能.与目前的合成方法相比,CPO酶促氧化制备手性R-苄基甲基亚砜高效、定向,酶用量极少,具有一定的产业化应用潜能.     

Development and validation of a highly sensitive LC-MS/MS method for simultaneous quantitation of ethionamide and ethionamide sulfoxide in human plasma: application to a human pharmacokinetic study

A highly sensitive and specific LC‐MS/MS method has been developed for simultaneous quantification of ethionamide and ethionamide sulfoxide in human plasma (300 µL) using prothionamide as an internal standard (IS). Solid‐phase extraction was used to extract ethionamide, ethionamide sulfoxide and IS from human plasma. The chromatographic separation of ethionamide, ethionamide sulfoxide and IS was achieved with a mobile phase consisting of 0.1% acetic acid : acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a Peerless Basic C₁₈ column. The total run time was 3.5 min and the elution of ethionamide, ethionamide sulfoxide and IS occurred at 2.50, 2.18 and 2.68 min, respectively. A linear response function was established for the range of concentrations 25.7–6120 ng/mL (r > 0.998) for ethionamide and 50.5–3030 ng/mL (r > 0.998) for ethionamide sulfoxide. The intra‐ and inter‐day precision values for ethionamide and ethionamide sulfoxide met the acceptance as per FDA guidelines. Ethionamide and ethionamide sulfoxide were stable in battery of stability studies, viz. bench‐top, autosampler and freeze–thaw cycles. The developed assay was applied to a pharmacokinetic study in humans. Copyright © 2011 John Wiley & Sons, Ltd.     

An NMR-Based Biosensor to Measure Stereospecific Methionine Sulfoxide Reductase Activities in Vitro and in Vivo**

Oxidation of protein methionines to methionine-sulfoxides (MetOx) is associated with several age-related diseases. In healthy cells, MetOx is reduced to methionine by two families of conserved methionine sulfoxide reductase enzymes, MSRA and MSRB that specifically target the S- or R-diastereoisomers of methionine-sulfoxides, respectively. To directly interrogate MSRA and MSRB functions in cellular settings, we developed an NMR-based biosensor that we call CarMetOx to simultaneously measure both enzyme activities in single reaction setups. We demonstrate the suitability of our strategy to delineate MSR functions in complex biological environments, including cell lysates and live zebrafish embryos. Thereby, we establish differences in substrate specificities between prokaryotic and eukaryotic MSRs and introduce CarMetOx as a highly sensitive tool for studying therapeutic targets of oxidative stress-related human diseases and redox regulated signaling pathways.     

The oxysulfenylation of alkenes with dimethyl sulfoxide/oxalyl chloride

A convenient method for the oxysulfenylation of alkenes using dimethyl sulfoxide/oxalyl chloride is described. Cycloalkenes give trans-adducts stereospecifically. The reactions of styrene are highly regioselective for Markovnikov adducts, whereas aliphatic alkenes lead to anti-Markovnikov adducts mainly.     

Synthesis of polyacetylene with sulfoxide functions

Polyacetylene functionalized by sulfoxide groups was synthesized from poly(methyl vinyl sulfoxide) by the elimination of methanesulfenic acid under the action of a strong base at 20—50 °C.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 774–776, March, 2005.     

手性亚砜法立体选择性合成手性非洲蔗螟性信息素（＋）－Eldanolide

手性亚砜（＋）－Ｒ－手性烷基亚砜与巴豆酸甲酯进行不对称Ｍｉｃｈａｅｌ加成反应，立体选择性地合成了（＋）－Ｅｌｄａｎｏｌｉｄｅ，全合成的光学产率约为３９％，其顺、反异构体之比为８：９２。