沙蚕毒素和杀螟丹的神经毒性--直接封阻昆虫体内烟碱受体/通道

烟碱乙酰胆碱受体(nAChR)是由神经递质泵控制开合的离子通道，它由同系5个亚基组成，穿过突触膜。从nAChR亚基的结构推断它是亲水的胞外区域结构，胆碱能兴奋剂或竞争性封阻剂与受体结合的位点和4个跨膜疏水链段位于此结构中。此外，这5个亚基的另一个跨膜区域结构形成离子通道孔腔．非竞争性封阻剂(NCBs，离子通道封阻剂)     

以昆虫瞬时受体电位(TRP)通道作为杀虫剂及驱避剂的靶标

<正>昆虫瞬时受体电位(TRP)通道是离子通道的一大类别,在几乎所有的感觉系统中发挥关键的信号传导作用。其他离子通道类别,特别是电压依赖性离子通道、配体门控离子通道和细胞内钙释放通道(鱼尼汀受体)长期以来被认为是最成功的杀虫剂靶标。但是最近才发现,TRP通道是探索已久的某些取食抑制剂类杀虫剂的靶标,使这类通道和感觉过程成为杀虫剂靶标的开发热点。最近还发现驱避剂香茅醛可激活TRPA1通道。由于感受和响应外部和     

VNX-000440系列均三嗪类杀虫活性物质的发现和活性

ω-hexatoxin-Hv1a是蜘蛛体内存在的多肽毒素,是昆虫电压门控离子通道拮抗剂。建立了此物质的3D药效团模型,用计算机从已知的商品化物质数据库中筛选出了与药效团模型相匹配的物质,并进一步用Accelrys软件进行筛选。对选出的物质进行活性测定,均三嗪类物质VNX-000440是得到的一个活性物质。经结构修饰得到了对埃及伊蚊和甜菜夜蛾活性高的物质VNX-000443。经对蜚蠊DUM神经元离子通道的影响测定试验,发现此类物质对昆虫电压门控离子通道有抑制作用。     

全氟磺酸树脂在氯碱膜中的作用机理探析

根据氯碱膜电解的工作原理,分析了磺酸树脂层的微观结构,认为电驱动下的离子迁移与水传递是以水合离子通过膜通道的方式进行的。膜的离子交换基团主导离子簇和离子通道的形成。结合加工过程解释了离子通道的形成过程,提出曲折贯通的离子通道而非离子交换能力是磺酸层的主要作用机理。膜的离子透过性赋予膜以电导性,而离子的水传递数决定了氯碱膜的水通量大小。在膜中构建纳米通道可以为新一代氯碱膜的开发提供新的思路。     

可用于水处理的离子选择性纳米离子通道研究进展

选择性离子去除作为一种新兴的水处理方法,已被用于废水中的养分回收、水的软化、从盐水提取关键矿物质以及工业废水的利用等水处理领域。生物离子通道具有高效的单离子选择性,在过去的20 a里,纳米级和亚纳米级离子通道都被成功制备出来以模拟生物离子通道。主要介绍了天然离子通道的概念和理论框架,综述了目前纳米离子通道膜的材料与制备方法,总结了典型水污染离子的纳米离子通道选择性及优缺点和研究方向。单/多价离子之间的离子大小、电荷和亲疏水差异可测量,因此构建单/多价之间的离子选择性通道的基础是通道尺寸、表面电荷和亲疏水性的调节。而单价离子间尺寸差异并不显著,因此,特异性离子结合相互作用被引入到亚1 nm通道中以实现单离子选择性。分析了理想的纳米离子通道如何构建,提出目标离子选择性通常取决于通道的物理和化学性质,包括孔径、通道维度、表面电荷、功能位点和通道壁极性等,通过改变或优化这几种因素,可以提高膜对于目标离子的选择性分离。最后,对未来将膜技术与纳米离子通道结合以实现离子选择性去除进行了展望。     

γ-氨基丁酸门控氯离子通道受体及其靶标杀虫剂

作为半胱氨酸环配体门控离子通道超家族成员之一,γ-氨基丁酸门控氯离子通道(GABA-Cl)主要介导神经系统快速抑制性神经传递.由于其在昆虫和脊椎动物体内存在显著差异,GABA-Cl受体成为了现代杀虫剂研发的理想靶标.对GABA-Cl受体的结构和功能进行介绍,并对其靶标杀虫剂的研发背景与现状、化学合成、作用机制、生物活性...     

破伤风毒素的提纯及形成离子通道的特性

应用硫酸铵分段沉淀和 Ultrogei AcA_(34)凝胶过滤对破伤风毒进行了提纯,并对形成的离子通道在中毒作用中的功能进行了讨论。提纯的毒素与抗粗制毒素血清形成一条沉淀线,于聚丙烯酰胺凝胶电泳中形成单一的蛋白带,分子量为15万,等电点为5.95,毒力为1～3×10~4MLD/μg 蛋白。给小鼠注射低剂量毒素引起迟发性强直性痉挛;注射高剂量毒素引起快速的类肉毒毒素的松弛性麻痹,直至死亡。应用 Patch clamp 技术,破伤风毒素于人工磷脂膜上形成离子通道。只有当膜两侧存有 pH 梯度时毒素才形成离子通道,因此是 pH 依赖的。通道的电导系数为9 PS。     

植物离子通道农药潜在的作用靶标

离子通道是由与膜结合的蛋白质构成，离子通过它可以穿越没有渗透性的细胞膜。动物体内，离子通道最主要的作用是诱导神经细胞和心肌发挥作用。它们也能控制细胞体积的大小、细胞生长与分化以及神经递质的释放。     

电化学整流研究及应用进展

细胞膜上的离子通道是细胞与周围环境进行物质交换的重要途径,而对离子通道的"掌控"起决定性作用的正是电化学整流。电化学整流的研究对于深入理解细胞膜离子通道的作用机理,以及仿生纳米器件的构筑具有非常重要的科学意义和应用价值。从体系构建到机理推导直至应用这几个方面对国内外课题组有关电化学整流的研究进行了综述,并展望了其未来的发展方向。     

1,2,4-噁二唑和1,2,4-噻二唑衍生物的合成和杀虫活性

乙酰胆碱受体(AChR)含有神经递质乙酰胆碱(ACh)的结合点和阳离子跨膜离子通道.所有的乙酰胆碱受体除能被乙酰胆碱激活外,其也可与其他分子,如烟碱和毒蕈碱作用.烟碱乙酰胆碱受体(nAChRs)特别能与烟碱作用,并已知为离子型乙酰胆碱受体(配体门控离子通道);相比,而毒蕈碱乙酰胆碱受体(mAChRs)则特别能与毒蕈碱作用,亦得知为代谢型乙酰胆碱受体(非离子通道).烟碱乙酰胆碱受体和毒草碱乙酰胆碱受体是2种主要的胆碱能受体.     

Expanding the small molecular toolbox to study big biomolecular machines

Ion channels are transmembrane protein complexes that are found in virtually all cells. They fulfill a crucial physiological function by facilitating communication between and within cells. Consequently, impaired channel function, e.g. due to mutations, often has profound physiological effects. Their central role in cell-to-cell communication makes ion channels formidable drug targets, albeit their transmembrane nature often hampers efforts to obtain high resolution structures and hence impedes drug discovery. Decades of electrophysiology and molecular biology studies have made critical contributions to our understanding of ion channel structure and function. Small organic compounds, acting as either agonist or antagonist, have played vital roles in such studies and in recent years these molecular tools have become more sophisticated. Decorated with fluorescent, photoaffinity and/or affinity tags small molecular tools enable imaging, binding site mapping and isolation of biomolecular targets. Here, some of the methodologies employed in the context of ion channels are discussed and highlighted with representative examples.     

Methods of Measuring Mitochondrial Potassium Channels: A Critical Assessment

In this paper, the techniques used to study the function of mitochondrial potassium channels are critically reviewed. The majority of these techniques have been known for many years as a result of research on plasma membrane ion channels. Hence, in this review, we focus on the critical evaluation of techniques used in the studies of mitochondrial potassium channels, describing their advantages and limitations. Functional analysis of mitochondrial potassium channels in comparison to that of plasmalemmal channels presents additional experimental challenges. The reliability of functional studies of mitochondrial potassium channels is often affected by the need to isolate mitochondria and by functional properties of mitochondria such as respiration, metabolic activity, swelling capacity, or high electrical potential. Three types of techniques are critically evaluated: electrophysiological techniques, potassium flux measurements, and biochemical techniques related to potassium flux measurements. Finally, new possible approaches to the study of the function of mitochondrial potassium channels are presented. We hope that this review will assist researchers in selecting reliable methods for studying, e.g., the effects of drugs on mitochondrial potassium channel function. Additionally, this review should aid in the critical evaluation of the results reported in various articles on mitochondrial potassium channels.     

Structural Modelling of KCNQ1 and KCNH2 Double Mutant Proteins,Identified in Two Severe Long QT Syndrome Cases,Reveals New Insights into Cardiac Channelopathies

Congenital long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of the QT interval and T-wave abnormalities, caused, in most cases, by mutations in KCNQ1, KCNH2, and SCN5A. Although the predominant pattern of LQTS inheritance is autosomal dominant, compound heterozygous mutations in genes encoding potassium channels have been reported, often with early disease onset and more severe phenotypes. Since the molecular mechanisms underlying severe phenotypes in carriers of compound heterozygous mutations are unknown, it is possible that these compound mutations lead to synergistic or additive alterations to channel structure and function. In this study, all-atom molecular dynamic simulations of KCNQ1 and hERG channels were carried out, including wild-type and channels with compound mutations found in two patients with severe LQTS phenotypes and limited family history of the disease. Because channels can likely incorporate different subunit combinations from different alleles, there are multiple possible configurations of ion channels in LQTS patients. This analysis allowed us to establish the structural impact of different configurations of mutant channels in the activated/open state. Our data suggest that channels with these mutations show moderate changes in folding energy (in most cases of stabilizing character) and changes in channel mobility and volume, differentiating them from each other and from WT. This would indicate possible alterations in K⁺ ion flow. Hetero-tetrameric mutant channels showed intermediate structural and volume alterations vis-à-vis homo-tetrameric channels. These findings support the hypothesis that hetero-tetrameric channels in patients with compound heterozygous mutations do not necessarily lead to synergistic structural alterations.     

Perspectives on Potential Fatty Acid Modulations of Motility Associated Human Sperm Ion Channels

Human spermatozoan ion channels are specifically distributed in the spermatozoan membrane, contribute to sperm motility, and are associated with male reproductive abnormalities. Calcium, potassium, protons, sodium, and chloride are the main ions that are regulated across this membrane, and their intracellular concentrations are crucial for sperm motility. Fatty acids (FAs) affect sperm quality parameters, reproductive pathologies, male fertility, and regulate ion channel functions in other cells. However, to date the literature is insufficient to draw any conclusions regarding the effects of FAs on human spermatozoan ion channels. Here, we aimed to discern the possible effects of FAs on spermatozoan ion channels and direct guidance for future research. After investigating the effects of FAs on characteristics related to human spermatozoan motility, reproductive pathologies, and the modulation of similar ion channels in other cells by FAs, we extrapolated polyunsaturated FAs (PUFAs) to have the highest potency in modulating sperm ion channels to increase sperm motility. Of the PUFAs, the ω-3 unsaturated fatty acids have the greatest effect. We speculate that saturated and monounsaturated FAs will have little to no effect on sperm ion channel activity, though the possible effects could be opposite to those of the PUFAs, considering the differences between FA structure and behavior.     

配合物K2[Y^Ⅲ（dtpa）（H2O）]·7H2O的合成及结构研究

介绍了稀土金属离子Y^Ⅲ与氨基多羧酸类配体二乙三胺五乙酸（dtpa）形成的配合物的分子结构。配合物K2[Y^Ⅲ（dtpa）（H2O）]·7H2O中Y^Ⅲ与来自同一个二乙三胺五乙酸的3个氮原子和5个羧基氧原子及一个水分子的氧原子配位,配位数为9,形成单帽四方反棱柱体结构。     

Integrated sensitive on-chip ion field effect transistors based on wrinkled InGaAs nanomembranes

Self-organized wrinkling of pre-strained nanomembranes into nanochannels is used to fabricate a fully integrated nanofluidic device for the development of ion field effect transistors (IFETs). Constrained by the structure and shape of the membrane, the deterministic wrinkling process leads to a versatile variation of channel types such as straight two-way channels, three-way branched channels, or even four-way intersection channels. The fabrication of straight channels is well controllable and offers the opportunity to integrate multiple IFET devices into a single chip. Thus, several IFETs are fabricated on a single chip using a III-V semiconductor substrate to control the ion separation and to measure the ion current of a diluted potassium chloride electrolyte solution.     

The hERG Potassium Channel and Drug Trapping: Insight from Docking Studies with Propafenone Derivatives

The inner cavity of the hERG potassium ion channel can accommodate large, structurally diverse compounds that can be trapped in the channel by closure of the activation gate. A small set of propafenone derivatives was synthesized, and both use‐dependency and recovery from block were tested in order to gain insight into the behavior of these compounds with respect to trapping and non‐trapping. Ligand–protein docking into homology models of the closed and open state of the hERG channel provides the first evidence for the molecular basis of drug trapping.     

蛋白质化学修饰的研究进展

蛋白质分子具有极其复杂的结构层次，用化学修饰的方法研究蛋白质分子的结构与功能的关系一直是生物化学和分子生物学领域的热点。人们研究出许多小分子化学修饰剂并进行了多种类型的化学修饰。综述了蛋白质化学修饰领域的研究现状与水平，同时强调蛋白质的化学修饰是生化药物研究开发的重要手段之一。