DCN1-UBE2M相互作用抑制剂的3D-QSAR、分子对接和分子动力学研究

类泛素化是一种蛋白质翻译后修饰,其异常会导致神经退行性疾病和多种肿瘤的发生,因此它被视为有希望的抗肿瘤靶标。研究表明,抑制DCN1-UBE2M相互作用可选择性阻遏类泛素化。本文基于哌啶基脲类DCN1-UBE2M相互作用抑制剂进行3D-QSAR、分子对接和分子动力学模拟研究。利用3D-QSAR中的CoMFA和CoMSIA方法构建了相关模型,其交叉验证系数q~2分别为0.686、0.682,拟合验证系数r~2分别为0.966、0.931,表明模型是可靠的且预测能力较好。接着运用分子对接分析哌啶基脲类化合物与DCN1的相互作用,结果表明,它们主要通过氢键和疏水作用与靶蛋白结合。通过分子动力学模拟研究进一步了解结合模型和验证对接结果。本文所得的研究结果可为今后此类化合物的结构优化提供有效信息。     

Enantiomeric Separation of Nefopam Hydrochloride by Affinity Electrokinetic Chromatography Using Chondroitin Sulfate A as Chiral Selector and Its Chiral Recognition Mechanism

In this study, a new approach to the enantioseparation of nefopam hydrochloride by means of affinity electrokinetic chromatography (AEKC) with chondroitin sulfate A belonging to linear ionic polysaccharides has been developed. The difference in the antinociceptive activity of the enantiomers of nefopam was demonstrated in some studies, and the method established in this paper allowed complete separation of nefopam. Especially, there are no reports concerned with the enantioselective separation of nefopam using chondroitin sulfate A as chiral selectors in CE. During the course of this work, both migration time and enantioseparation of nefopam were influenced by several parameters such as pH of the BGE, selector concentration, capillary temperature and applied voltage. Consequently, these parameters were systematically optimized in order to obtain the optimum enantioseparation of nefopam. Moreover, comparison of the influences of the studied parameters was further investigated using univariate analysis of variance as a calculation method by Statistical Product and Service Solutions (SPSS) in this paper. Finally, a mechanism of enantiorecognition in AEKC towards the enantiomers of nefopam with chondroitin sulfate A was described.     

Study on clarithromycin lactobionate based dual selector systems for the enantioseparation of basic drugs in capillary electrophoresis

In this paper, the use of clarithromycin lactobionate, a kind of antibiotic chiral selector, in combination with four neutral cyclodextrin derivatives (glucose‐β‐cyclodextrin, hydroxyethyl‐β‐cyclodextrin, methyl‐β‐cyclodextrin and hydroxypropyl‐β‐cyclodextrin) was reported for the first time. As a result, these dual systems gave much better resolution of nefopam (the Rs increased to 3.58, 2.72, 1.49 and 1.42, respectively) compared to the single systems. The effects of buffer pH and selector concentration on the separation of nefopam were also investigated. Additionally, some other basic drugs including metoprolol, atenolol, propranolol, bisoprolol, esmolol and ritodrine were tested for the investigation and evaluation of the enantiorecognition capability of the four dual systems. As expected, the synergistic effect was observed in four systems. Different results of these dual systems were also summarized.     

Study of the enantioseparation capability of chiral dual system based on chondroitin sulfate C in CE

It has been reported that chiral dual system is able to improve the enantioseparation of enantiomers in many cases. Currently, the dual systems involved in CE chiral separation are mostly dual CDs systems, and the polysaccharides‐based chiral dual system was reported in only one paper. To the best of our knowledge, the use of chondroitin sulfate C (CSC)‐based dual system for enantiomeric separation has not been reported previously. Herein, four CSC‐based chiral dual systems, namely CSC/glycogen, CSC/chondroitin sulfate A (CSA), CSC/hydroxypropyl‐β‐CD (HP‐β‐CD), as well as CSC/β‐CD (β‐CD), were evaluated for the first time for their enantioseparation capability by CE in this paper. During the course of the work, the influences of chiral selector concentration and buffer pH values on enantioseparation in dual systems were systematically investigated. Under the optimized conditions, the dual system consisting of CSC and glycogen exhibited better separations toward nefopam, duloxetine, sulconazole, atenolol, laudanosine, and cetirizine enantiomers compared to the single CSC or glycogen system. The combination of CSC and HP‐β‐CD improved the separation of amlodipine and chlorphenamine enantiomers. However, no synergistic effect was observed in the CSC/CSA and CSC/β‐CD systems.     

HIFRL首次在束γ实验

在兰州重离子加速器(HIRFL)上调试完成了一套在束γ核结构研究装置:SFC(ECR源)+直通管道(限束狭缝)+在束γ终端,并进行了首次在束γ实验,各项在束实验的指标,特别是中子、γ本底达到了较为理想的水平. 对¹⁶O轰击¹⁹⁷Au反应进行了在束γ测量,包括γ单谱、γ激发函数、γ角分布和γ-γ-t符合,在一些测量中,采用了独特的技术.     

对羧基偶氮羧与钙的β型显色反应研究及应用

本文建立了对羧基偶氮羧分光光度法测定微量钙的方法,研究了试剂与钙的β型显色反应的条件、影响因素及形成机理。在柠檬酸介质中,钙与该试剂只发生灵敏的β型显色反应,络合物最大吸收波长为718nm(△λ=157nm),表观摩尔吸光系数ε=1.51×10~5L·mol~(-1)·cm~(-1),反应完全后,吸光度可保持4h不变。方法用于直接测定复方氯化钠注射液中的钙,回收率在99.20％～103.5％之间,结果与标准方法一致,相对标准偏差小于1.5％。     

经(NaPO3)6溶液处理的硫酸钙矿石表面的电子能谱研究

本文用XPS和AES测试研究了经(NaPO3）6水溶液处理后的岩盐矿中的硫酸钙矿石表面性质变化一表面元素种类、各元素的原子百分比、元素价态及可能的结合方式，韧步探明了(NaPO3)6对CaSO4的阻溶作用机理，为充分揭示该过程机理提供了重要依据。     

间氯偶氮安替比林流动注射分析测定药物及水中钙

基于间氯偶氮安替比林可与钙在碱性介质中形成灵敏的兰色络合物这一显色反应，本文在自行组装的带微型计算机的流动注射分析仪上，以分光光度计作检测器，建立了测定微量钙的流动注射分光光度法。最佳显色反应条件：０．０８ｍｏｌ／Ｌ ＮａＯＨ－０．０１２％显色剂２．０％三乙醇胺溶液，测定波长为６３０ｎｍ。以三乙醇胺为掩蔽剂，方法选择性较高。钙的线性范围为１．０￣１５．０μｇ／ｍｌ，检测限０．５μｇ／ｍｌ，进样频率