硝西泮中一种未知杂质的结构确证

目的: 对硝西泮原料药中一种未知杂质进行结构确证.方法: 应用HPLC-MS/MS、核磁共振(1H-NMR、13C-NMR) 技术,对硝西泮原料药中一种未知杂质进行结构分析.结果: 首次发现并确定硝西泮未知杂质的结构.结论: 该方法可为硝西泮的质量控制提供依据.     

降糖新药那格列奈的一种新晶型结构

目的：发现降糖药那格列奈另一种新的晶型结构,我们称之为S型。给出X射线衍射图谱和相关数据。方法：用X射线衍射物相分析法确定这种新的结构。用差示扫描量热仪测定它的熔点。结果：S型那格列奈具有与文献报道的H、B型完全不同的晶体结构。熔点为172．04℃,。结论：S型那格列奈是一种新型结构,X射线衍射法是药物晶型结构鉴定的有效方法。     

改进的势能曲面变平法在二维非格点模型中的应用

蛋白质结构预测问题是生物信息学中的一个重要问题.缺少一种有效的全局寻优方法是阻碍这一问题解决的关键.势能曲面变平(ELP)法是一种启发式的全局优化方法,是一种推广的Monte Carlo方法,已成功地应用于许多优化问题.在ELP法的基础上,提出了改进的势能曲面变平(ELP )算法.将ELP 算法应用于二维非格点的蛋白质AB模型,预测和发现四条链长分剐为13,21,34和55的氨基酸序列的蛋白质结构.数值实验表明,ELP 算法是一种预测蛋白质结构的有效算法.     

非甾体抗炎药联苯乙酸的简便合成方法

目的探索联苯乙酸的一种新的合成方法。方法以苯硼酸和对溴苯乙酸乙酯为起始原料,经偶联、皂化二步反应得目标化合物。结果化合物的结构经IR1、HNMR分析确证。结论合成路线较短,反应条件温和、易控制,二步总收率达78%,是合成该目标化合物的一种较为理想的方法。     

调血脂药阿托伐他汀钙的合成研究进展

综述治疗高脂血症的他汀类药物阿托伐他汀钙的合成方法,根据文献报道归纳出阿托伐他汀钙的合成路线有两种,一种是先合成出取代的吡咯环,然后在环上引入手性的3,5-顺式双羟基庚酸结构（线性合成）,一种是先制备手性的3,5-顺式二羟基庚酸片断,然后与1,4-二羰基化合物环合得到吡咯环结构（汇聚合成）。还比较了各合成工艺方法的优缺点,为寻找一条适合大规模、工业化生产的工艺路线提供参考。     

鼻内镜下手术治疗鼻腔多结构异常的疗效观察

目的分析鼻内镜下手术治疗鼻腔多结构异常的方法及疗效。方法采用鼻内镜下鼻中隔成形术、中鼻甲成形术、下鼻甲成形术、前组筛窦开放术等治疗鼻腔多结构异常130例。结果随访3～6月,治愈102例,有效26例,无效2例,总有效率98.5%。结论鼻内镜下手术治疗鼻腔多结构异常是一种安全有效方法。     

中成药中非法添加他达拉非新型衍生物的检测及结构鉴定

目的对中成药中非法添加的一种新型他达拉非类衍生物进行结构确证。方法采用制备液相分离、纯化目标物,采用高效液相色谱法、液相色谱-质谱联用技术、核磁共振氢谱技术等手段对其结构进行表征,并结合文献报道,推断该化合物的结构。结果通过数据分析与文献报道,确定该化合物为一种新型的他达拉非类衍生物。结论该化合物为一种新型的他达拉非衍生物,在国内现行的PDE5型抑制剂检测标准中均未收载。本研究为进一步完善PDE5型抑制剂检测标准提供了科学依据。     

一种新型多金属氧酸盐（Himi）2〔SMo12O40〕·（imi）2·H2O的合成及晶体结构

目的合成一种新型多金属氧酸盐并加以结构解析。方法以钼酸、咪唑和硫酸钠采用水热法反应,利用X-射线衍射对单晶产物进行表征。结果得到一种新型十二钼硫酸化合物,表征了其结构。结论制备了一种新型＂Keggin＂型多金属氧酸盐（Himi）2〔SMo12O40〕（imi）2H2O（imi=咪唑）1,为后续的生物活性研究打下基础。     

化学分类与高等植物中抗癌活性成分的寻找

<正> 一、高等植物抗癌活性成分研究的一般情况一般认为,寻找新的抗癌化疗新药的方法有两种:一种是从天然产物(植物及微生物的代谢产物)中分离具有抗癌活性的成分,所分出的原成分不合适者再进行部分结构改造,如含量甚微的尚须进行全合成,使之成为毒性低,易于吸收的产物。此法所需材料来自民间土方、验方、植物科属、植物化学成分及随机抽样等;第二种方法是利用化学合成制备新的抗癌药物的方法。此法的基本原理是根据已有的资料认为与活性有关的官能团适当组合起来得出一种化合物。但由于生理活性物质的结构与活性之间的关系目前并不十分清楚,因此,从概率上看,第一种方法要比第二种方法大得多。     

基于PDMS自组装褶皱结构的近红外亚波长金属偏振光栅设计分析

提出一种以聚二甲基硅氧烷(PDMS)为基底,结合氧气等离子体氧化处理在PDMS表面生成类二氧化硅刚性层,通过聚对苯二甲酸乙二醇酯(PET)柔性薄膜谐调应力在柔性衬底/刚性薄膜的表面自组装形成有序结构的方法。并制备了周期450 nm、占空0.5、高度100 nm的有序的亚波长正弦光栅结构,以此为基底设计了可用于近红外的金属偏振光栅。结合不同的金属纳米薄膜沉积方法,以严格耦合波理论为分析基础,分析了这三种光栅在近红外波段的偏振性能。分析结果表明,金属层的结构对光栅的偏振性能影响很大,三种结构各有优劣。这种基于自组装结构的加工方法有望解决亚波长金属光栅生产周期长、生产成本高的问题。     

药物化学结构在线分析系统

高通量的筛选药物结构数据库,可以辅助药物设计。该文从DrugBank数据库获取4 886种药物的化学结构信息,建立了一个免费的在线药物化学结构分析平台。基于Tanimoto系数预先计算了药物两两化学结构相似性矩阵作为后台数据,从而提高了高通量药物结构分析的速度。该平台实现了药物通用名、商品名和别名的检索,药物化学结构相似性搜索查看及其聚类分析可视化的功能。应用该系统进一步验证了与相同靶蛋白关联的药物,其化学结构更相似的结论。本文系统可通过http://122.70.220.99/bme的Drug and Disease访问。     

Small artery remodelling in hypertension

Increased blood pressure (essential hypertension) is associated with increased cardiovascular risk, and the condition is treated primarily with a view to reducing this parameter. However, in the early stages, the main pathological changes are increased peripheral resistance and altered cardiovascular structure. The aim of this MiniReview was to trace the endeavours over the past several decades to translate these findings into answering the question whether normalization of resistance vessel structure should be a target for therapy. This MiniReview describes first the altered structure of the resistance vasculature in essential hypertension, where the vessels show increased media/lumen ratio because of inward eutrophic remodelling. Secondly, evidence is presented that altered small artery structure appears to have prognostic consequences. Then, the cellular mechanisms that may be involved are discussed, where there is evidence that vasoconstriction in itself can cause inward remodelling and that this can be prevented by vasodilators. This leads to a discussion of the degree to which it may be possible to rectify the abnormal structure, where it appears that this may be achieved using a therapy that causes vasodilatation in the patient concerned. Finally, the consequences of these findings are considered as regards clues for strategies that may be able to improve the outcome of antihypertensive therapy. The MiniReview concludes that there is reasonably strong evidence that improvement in abnormal resistance vessel structure requires a treatment that reduces peripheral resistance in the individual patient.     

甲状旁腺激素构效关系的研究进展

甲状旁腺激素(PTH)是生物体内调节钙、磷代谢最为重要的肽类激素之一,其氨基端1-34片段具有全分子PTH与受体结合的能力及生物活性,被广泛用于研究PTH的结构与功能。PTH二级结构中富含α-螺旋,该螺旋结构在PTH与受体相互作用中起重要作用,其中羧基端负责与受体结合,氨基端负责生理活性。现从甲状旁腺激素的结构、与受体的相互作用和构效关系等角度出发,综述了甲状旁腺激素近年来的研究状况,为开发新型骨质疏松症治疗药物提供理论依据。     

COMPARATIVE THEORETICAL CONFORMATIONAL ANALYSIS OF THE INSULIN A6-A11 PEPTIDES

The insulins of pig, ox, horse and goat differ only by the cyclic A6-A11 peptide which is thought to be an antigenic determinant of the molecule. The structure of the four peptides is investigated by conformational energy calculations in order to verify whether a common backbone conformation can be found for all four species, the antigenic difference being consequently due only to the difference in the side chains exposed to the solvent, or whether each sequence gives rise to a preferential backbone conformation, which would lead to the conclusion that the antigenic difference is conveyed by a more pronounced difference in the molecular structure. From the results of the study on the isolated peptides, it appears that an energetically favourable backbone conformation common to all four species can be found. This conformation is compared with the structure deduced from the X-ray diffraction data available for pig insulin.     

PI3K/mTOR双重抑制剂的研究进展

磷脂酰肌醇3-激酶/哺乳动物雷帕霉素靶蛋白(phosphoinosmde-3-kinase/the mammalian target of rapamycin,PI3K/mTOR)双重抑制剂已经成为抗肿瘤药物研发的热点之一。本文介绍芳基脲类和3-吡啶基杂环类等PI3K/mTOR双重抑制剂的化学结构,根据其结构特点及其与PI3Kγ共结晶模式,剖析了两类抑制剂药效团的基本结构。     

Structural genomics and the metabolome: combining computational and NMR methods to identify target ligands

One of the goals of structural genomics is to use three-dimensional structures to gain insights into the function of poorly understood or hypothetical proteins. Approximate functions are often apparent from the protein fold, but more precise biochemical functions are difficult to obtain from the structure alone. Analysis of the structure using a variety of informatics tools can lead to the identification of possible binding sites for small molecules. This knowledge can be used in combination with molecular docking and nuclear magnetic resonance screening methods to identify candidate target ligands for proteins of previously unknown function.     

核糖体失活蛋白抗血液病肿瘤的研究

核糖体失活蛋白是广泛存在于高等植物中能抑制核糖体翻译功能的一类毒蛋白。它能够对哺乳动物拔糖体大亚基上的28SrRNA进行脱嘌呤作用。从而破坏技糖体的结构。抑制蛋白质的生物合成。本文就核糖体失活蛋白的生物学活性以及近年来在抗血液病肿瘤方面的研究进展做一综述。     

X-ray crystallography: Assessment and validation of protein-small molecule complexes for drug discovery

INTRODUCTION: Crystallography is the key initial component for structure-based and fragment-based drug design and can often generate leads that can be developed into high potency drugs. Therefore, huge sums of money are committed based on the outcome of crystallography experiments and their interpretation. AREAS COVERED: This review discusses how to evaluate the correctness of an X-ray structure, focusing on the validation of small molecule-protein complexes. Various types of inaccuracies found within the PDB are identified and the ramifications of these errors are discussed. The reader will gain an understanding of the key parameters that need to be inspected before a structure can be used in drug discovery efforts, as well as an appreciation of the difficulties of correctly interpreting electron density for small molecules. The reader will also be introduced to methods for validating small molecules within the context of a macromolecular structure. EXPERT OPINION: One of the reasons that ligand identification and positioning, within a macromolecular crystal structure, is so difficult is that the quality of small molecules widely varies in the PDB. For this reason, the PDB can not always be considered a reliable repository of structural information pertaining to small molecules, and this makes the derivation of general principles that govern small molecule-protein interactions more difficult.     

Coiled-coils: stability,specificity, and drug delivery potential

The coiled-coil is a ubiquitous protein folding and assembly motif made of alpha-helices wrapping around each other forming a supercoil. The sequences of coiled-coils are made of seven-residue repeats, called heptads, and thus are polymer-like. Due to its simplicity and regularity, the coiled-coil is the most extensively studied protein motif. In this review, results on coiled-coil stability and specificity from structural and biophysical studies are summarized. It is pointed out that the primary sequences of coiled-coils over specify the secondary structure but under specify the tertiary/quaternary structure. This leads to two unique features of coiled-coil structure: linkage between stability and specificity and decoupling of secondary and tertiary/quaternary structural specificity. This is followed by a discussion of the potential of coiled-coils as drug delivery vehicles, particularly the prospect in two-staged pretargeted delivery. Such potentials are intimately related to the unique structural features of coiled-coils. The aim of this review is to illustrate how knowledge on protein stability and specificity can be used in the de novo design of peptide-based drug delivery vehicles with well-defined structure and interaction features.