The first structurally analysed nucleic acid building block containing the Reese protecting group: 2′‐O‐[1‐(2‐fluorophenyl)‐4‐methoxypiperidin‐4‐yl]‐β‐D‐(1′R,2′R,3′R,4′R)‐uridine

The title compound, C₂₁H₂₆FN₃O₇, is assembled by N—H...O and O—H...O hydrogen bonds into well‐separated two‐dimensional layers of about 15 Å thickness. The crescent conformation of the molecules is stabilized by weak intramolecular C—H...O and C—H...F hydrogen bonds. The uridine moiety adopts an anti conformation. The ribofuranose ring exists in an envelope conformation. All the endocyclic uracil bonds are shorter than normal single C—N and C—C bonds, and five of them have comparable lengths, which implies a considerable degree of delocalization of the electron density within this ring.     

高效液相色谱法分析谷氨酸棒杆菌细胞内尿苷二磷酸葡萄糖和尿苷二磷酸半乳糖

建立了利用高效液相色谱分离分析谷氨酸棒杆菌细胞内尿苷二磷酸(UDP)葡萄糖与UDP半乳糖的新方法,考察了不同色谱柱、不同分离模式及不同流动相组成对UDP葡萄糖和UDP半乳糖的保留特性及分离度的影响。结果表明,在Zorbax NH2柱(250 mm×4.6 mm i.d.,5 μm)上以0.125 mol/L KH2PO4缓冲液(pH 3.6)-乙腈(体积比为40∶60)溶液为流动相,可使谷氨酸棒杆菌细胞内的两种中间代谢产物UDP葡萄糖与UDP半乳糖在22 min内达到基线分离。该方法对UDP葡萄糖和UDP     

含取代苯甲酰基硫脲的核苷类化合物的合成及杀菌活性研究

为了发现具有杀菌活性的新型先导化合物,基于几丁质合成酶催化作用机制,通过活性亚结构拼接方法,保留多氧霉素和尼克霉素中的活性尿苷部分,将具有良好杀菌活性的硫脲基团引入,设计合成了一系列含硫脲结构的核苷类化合物.以尿苷为原料,经5步反应制得目标物,其结构经IR,1H NMR及元素分析确证.初步生测结果表明,部分化合物对芦笋茎枯病(Phomopsisasparagi bubak)表现出明显的抑制活性,其中6m的抑制率在50μg/mL浓度下为97.2%,与相同浓度的多氧霉素B活性(100%)接近.     

新型芳基修饰的尿苷型荧光探针的合成及其性能

4-氟苯乙酮经二氧化硒氧化得到4-氟苯甲酰甲酸(1); 1与盐酸氨基脲在碱性条件下经环合反应制得5-(4-氟苯基)-6-氮杂嘧啶(2); 2与1-乙酰氧基-2,3,5-三苯甲酰氧基-1-β-D-呋喃核糖在无水乙腈中反应得2′,3′,5′-三苯甲酰氧基-5-(4-氟苯基)-6-氮杂尿苷(3); 3在甲醇中水解合成了一种新型荧光核苷探针--5-(4-氟苯基)-6-氮杂尿苷(4),其结构经¹H NMR, ¹³C NMR和MS(ESI)表征。并研究了4的性能。结果表明：4在水中的量子产率高达0.81,对极性变化敏感;4可选择性识别Pd²⁺,在5.0×10^-7~5.0×10^-6 mol·L^-1能定量检测Pd²⁺。     

Quantitative determination of uridine in rabbit plasma and urine by liquid chromatography coupled to a tandem mass spectrometry

Recently a pyrimidine nucleoside, uridine, has been show to have a protective effect on cultured human corneal epithelial cells, and on dry eye animal model and patients. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry method for the determination of uridine in rabbit plasma and urine. After protein precipitation with methanol including methaqualone (internal standard), the analyte was chromatographed on a reversed-phase column with a mobile phase of 0.1% formic acid aqueous solution and methanol (1:4, v/v). The accuracy and precision of the assay were in accordance with Food and Drug Administration regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of uridine in plasma and urine after a single oral administration of 450 mg/kg uridine in rabbits.     

Synthesis and characterization of mixed ligand complexes of bio-metals with pyrimidine nucleoside (uridine) and amino acids

The mixed ligand complexes of Cu(II), Ni(II) and Co(II) with uridine and amino acids, L-alanine, L-phenylalanine and L-tryptophan were synthesized and characterized by elemental analysis, conductivity data, infrared spectra, electronic spectra and magnetic susceptibility data. In these complexes, the nucleoside (uridine) acts as a monodentate ligand coordinating through O(4) under the conditions of investigation, whereas the amino acids coordinate through the carboxylate oxygen and the amino nitrogen. Distorted octahedral geometry for Cu(II) and octahedral geometries for both Ni(II) and Co(II) are proposed.     

Electrochemistry/mass spectrometry as a tool in metabolism studies—A review

The combination of electrochemistry (EC) and mass spectrometry (MS) has become a more and more frequently used approach in metabolism studies in the last decade. This review provides insight into the importance of metabolism studies during the drug development process and gives a short overview about the conventionally used methods since electrochemistry is often intended to substitute or minimize animal-based studies. The optimization of the electrochemical conditions is of great importance for a successful comparison with in vitro approaches. The type of metabolism reactions, which can be simulated by EC, has been extended with new cell types and working electrodes. Although the mechanism differs from the enzyme-catalyzed turnover, electrochemistry can be used to simulate a significant number of the respective reactions.     

尿苷二磷酸葡萄糖的合成研究进展

介绍了化学和酶法合成尿苷二磷酸葡萄糖(UDPG)及酶法合成13C标记UDPG的方法的优缺点及研究进展.     

Possible Role of Carboxyl and Imidazole Groups in the Catalysis of Pummelo Limonoid Glucosyltransferase

 Limonoid bitterness is a serious problem in the citrus industry worldwide. Limonoid glucosyltransferase is an enzyme that catalyzes the conversion of bitter limonoid into non-bitter limonoid glucoside while retaining the health benefit of limonoids in the juice. The immobilization of this enzyme in a column can solve the juice bitterness problem. More information about the catalytic residues of the en-zyme is needed in this immobilization process. Glutamate/aspartate, histidine, lysine, tryptophan, serine, and cysteine residues were chemi-cally modified to investigate their roles in the catalytic function of limonoid glucosyltransferase. Inactivation of the enzyme following modi-fication of carboxyl and imidazole moieties was a consequence of a loss in substrate binding and catalysis in the glucosyltransfer reaction. The modification of a single histidine residue completely destroyed the ability of limonoid glucosyltransferase to transfer the D-glucopyranosyl unit. Tryptophan seemed to have some role in maintaining the active conformation of the catalytic site. Lysine also seemed to have some direct or indirect role in this catalysis but the modification of serine and cysteine did not have any effect on catalysis. There-fore, we conclude that the carboxyl and imidazole groups contain amino acids are responsible for the catalytic action of the enzyme.     

尿嘧啶核苷酸阴离子液相中的过电子附着和电离

本文采用QM/MM方法研究液相尿嘧啶核苷酸阴离子的过电子附着和电离过程. 从分子动力学模拟的轨线抽取了40个采样结构,并计算了在这些采样点的垂直电子亲合势、绝热电子亲合势、垂直电子剥离能、垂直电离能和绝热电离能,分析了过电子附着和电离过程中的过电子及空穴分布. 模拟的垂直电子亲合势和绝热电子亲合势的平均值分别为-0.31 eV和2.13 eV,表明过电子很容易附着到尿嘧啶核苷酸阴离子上. 在尿嘧啶碱基上,垂直和绝热过电子分布的平均值分别为-0.50 eV和-0.62 eV,证明大多数的过电子局域在尿嘧啶碱基上. 双阴离子结构弛豫后,在几个抽样中发现过电子分布也可能会在碱基/糖环或者糖环/磷酸根上非局域化. 2.78 eV的垂直电子剥离能平均值表明,过电子附着后形成的尿嘧啶核苷酸双阴离子非常稳定. 液相尿嘧啶核苷酸阴离子的垂直电离能平均值为8.13 eV,与以前采用溶剂模型模拟的结果一致. 电离中,空穴主要分布在尿嘧啶碱基上,表明其最容易被电离. 在垂直电离中,几个抽样下的空穴会非局域分布在尿嘧啶碱基和糖环上. 绝热的空穴分布表明,在特定结构下,电离后的结构弛豫会导致磷酸根上电子和碱基上空穴转移到糖环上.