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Latek D Kolinski M Ghoshdastider U Debinski A Bombolewski R Plazinska A Jozwiak K Filipek S 《Journal of molecular modeling》2011,17(9):2353-2366
Cannabinoid and adrenergic receptors belong to the class A (similar to rhodopsin) G protein coupled receptors. Docking of
agonists and antagonists to CB1 and CB2 cannabinoid receptors revealed the importance of a centrally located rotamer toggle switch and its possible participation
in the mechanism of agonist/antagonist recognition. The switch is composed of two residues, F3.36 and W6.48, located on opposite
transmembrane helices TM3 and TM6 in the central part of the membranous domain of cannabinoid receptors. The CB1 and CB2 receptor models were constructed based on the adenosine A2A receptor template. The two best scored conformations of each receptor were used for the docking procedure. In all poses (ligand-receptor
conformations) characterized by the lowest ligand-receptor intermolecular energy and free energy of binding the ligand type
matched the state of the rotamer toggle switch: antagonists maintained an inactive state of the switch, whereas agonists changed it. In case of agonists of β2AR, the (R,R) and (S,S) stereoisomers of fenoterol, the molecular dynamics simulations provided evidence of different binding modes while preserving
the same average position of ligands in the binding site. The (S,S) isomer was much more labile in the binding site and only one stable hydrogen bond was created. Such dynamical binding modes
may also be valid for ligands of cannabinoid receptors because of the hydrophobic nature of their ligand-receptor interactions.
However, only very long molecular dynamics simulations could verify the validity of such binding modes and how they affect
the process of activation. 相似文献
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Isaac E. Marx Erin F. DiMauro Alan Cheng Renee Emkey Stephen A. Hitchcock Liyue Huang Ming Y. Huang Jason Human Josie H. Lee Xingwen Li Matthew W. Martin Ryan D. White Robert T. Fremeau Vinod F. Patel 《Bioorganic & medicinal chemistry letters》2009,19(1):31-35
A series of α-amidosulfones were found to be potent and selective agonists of CB2. The discovery, synthesis, and structure–activity relationships of this series of agonists are reported. In addition, the pharmacokinetic properties of the most promising compounds are profiled. 相似文献
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胶样菌CB39产海藻糖的研究 总被引:2,自引:0,他引:2
从长白山天池水中筛选到一株低温条件下产糖的细菌。通过薄层层析、成脎反应、毛细管等速电泳以及红外光谱法确定该糖为海藻糖;经鉴定此菌株是胶样菌属中的一个新种(ColloidesSp.)定名为CB39;与已报道的产海藻糖菌株不同的是,菌株CB39能将产生的海藻糖分泌到细胞外,18℃时其培养液中海藻糖含量为2562mg/g干菌体;采用紫外诱变法筛选到一株在25℃条件下产海藻糖量为4167mg/g干菌体的高产突变株5,产糖量是同温度下野生菌的8倍。 相似文献
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Background
The endogenous cannabinoid system is involved in the control of pain. However, little is known as to the integrity of the cannabinoid system in human pain syndromes. Here we investigate the expression of the cannabinoid receptor 1 (CB1) in human Achilles tendons from healthy volunteers and from patients with Achilles tendinosis.Methodology
Cannabinoid CB1 receptor immunoreactivity (CB1IR) was evaluated in formalin-fixed biopsies from individuals suffering from painful Achilles tendinosis in comparison with healthy human Achilles tendons.Principal Findings
CB1IR was seen as a granular pattern in the tenocytes. CB1IR was also observed in the blood vessel wall and in the perineurium of the nerve. Quantification of the immunoreactivity in tenocytes showed an increase of CB1 receptor expression in tendinosis tissue compared to control tissue.Conclusion
Expression of cannabinoid receptor 1 is increased in human Achilles tendinosis suggesting that the cannabinoid system may be dysregulated in this disorder. 相似文献6.
一株高毒力致病杆菌CB6的鉴定 总被引:8,自引:0,他引:8
从北京郊区果园采集的小卷蛾斯氏线虫(Steinernema carpocapsae)肠道内分离到一株具有较强杀虫和抑菌活性的致病杆菌菌株CB6。形态特征及生理生化特征测定结果表明,CB6菌株与致病杆菌属(Xenorhabdus)中的嗜线虫致病杆菌(X. nematophila)种的特征基本一致。测定了该菌株的16S rRNA序列并根据16S rRNA序列构建了系统发育树;在系统发育树中,CB6菌株与嗜线虫致病杆菌其他4个菌株形成一个类群,序列同源性大于99%。但CB6菌株的酪氨酸酶、脂酶(蛋黄)的产生、核糖产酸等生化特征与嗜线虫致病杆菌种内的其他菌株存在一定的差异,且具有更强的杀虫和抑菌活性。因此认为CB6菌株是嗜线虫致病杆菌的一个变种,命名为嗜线虫致病杆菌北京变种(X. nematophila var. pekingensis)。 相似文献
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Takao Kiyoi Mark York Stuart Francis Darren Edwards Glenn Walker Andrea K. Houghton Jean E. Cottney James Baker Julia M. Adam 《Bioorganic & medicinal chemistry letters》2010,20(16):4918-4921
Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure–activity relationships in the amide side chain of the indole C-3 position were also investigated. 相似文献
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《菌物学报》2017,(6):743-751
前期工作中采用组织分离法分离、纯化得到一白腐真菌CB1,本研究进一步观察菌株CB1形态特征和培养特性,克隆菌株CB1的ITS基因序列,对菌株CB1的ITS序列进行同源性比对和系统进化分析,完成菌株CB1综合的鉴定。同时对菌株CB1脱色两种活性染料进行了研究,探讨菌株CB1脱色活性染料的能力。结果表明,菌株CB1形态特征和培养特性与一色齿毛菌Cerrena unicolor特征基本吻合,菌株CB1的系统进化分析表明菌株CB1的ITS序列与一色齿毛菌的ITS序列有较近的进化关系,形态学和分子生物学综合鉴定菌株CB1为C.unicolor CB1。染料脱色结果表明,菌株CB1可以明显脱色活性黑和活性红染料,与脱色活性黑相比,菌株CB1可以更有效地脱色活性红染料,在脱色12d时,菌株CB1对浓度为10、50、100、250、500mg/L的活性黑脱色率分别为96%、93%、65%、55%、40%,菌株CB1对浓度为10、50、100、250、500mg/L的活性红在12d时的脱色率分别为98%、95%、91%、87%、83%。 相似文献
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Cannabinoid receptor Type 2(简称CB2)是大麻素受体的一种亚型,因为其无中枢神经副作用,不会产生成瘾性及耐受性,显示出了非常好的开发前景和潜在的应用价值。其作为免疫调节剂、神经保护剂和抗癌药等将具有巨大市场价值。目前,CB2蛋白的空间结构还未被测定出来,对于CB2的折叠问题研究也开展的较少,为了研究大麻素受体亚型蛋白CB2的折叠问题以及方便更多的研究人员对CB2空间结构和相关药理特性的研究,本文提出了一种基于HP模型的折叠求解方法。通过使用回溯机制和蒙特卡罗方法对此优化问题进行求解,算法可有效的在全局范围内进行寻找最优解,避免了掉入局部最优问题。实验结果表明,本文方法获取的CB2蛋白空间构象具有较低的能量值,折叠情况较好。 相似文献
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Exogenous and endogenous cannabinoids play an important role in modulating the release of neurotransmitters in hippocampal excitatory and inhibitory networks, thus having profound effect on higher cognitive and emotional functions such as learning and memory. In this study we have studied the effect of cannabinoid agonists on the potassium depolarization-evoked [(3)H]GABA release from hippocampal synaptosomes in the wild-type (WT) and cannabinoid 1 receptor (CB(1)R)-null mutant mice. All tested cannabinoid agonists (WIN55,212-2, CP55,940, HU-210, 2-arachidonoyl-glycerol, 2-AG; delta-9-tetra-hydrocannabinol, THC) inhibited [(3)H]GABA release in WT mice with the following rank order of agonist potency: HU-210>CP55,490>WIN55,212-2>2-AG>THC. By contrast, 2-AG and THC displayed the greatest efficacy eliciting almost complete inhibition of evoked [(3)H]GABA efflux, whereas the maximal inhibition obtained by HU-210, CP55,490, and WIN55,212-2 were less, eliciting not more than 40% inhibition. The inhibitory effect of WIN55,212-2, THC and 2-AG on evoked [(3)H]GABA efflux was antagonized by the CB(1) receptor inverse agonist AM251 (0.5 μM) in the WT mice. In the CB(1)R knockout mice the inhibitory effects of all three agonists were attenuated. In these mice, AM251 did not antagonize, but further reduced the [(3)H]GABA release in the presence of the synthetic agonist WIN55,212-2. By contrast, the concentration-dependent inhibitory effects of THC and 2-AG were partially antagonized by AM251 in the absence of CB(1) receptors. Finally, the inhibition of evoked [(3)H]GABA efflux by THC and 2-AG was also partially attenuated by AM630 (1 μM), the CB(2) receptor-selective antagonist, both in WT and CB(1) knockout mice. Our data prove the involvement of CB(1) receptors in the effect of exo- and endocannabinoids on GABA efflux from hippocampal nerve terminals. In addition, in the effect of the exocannabinoid THC and the endocannabinoid 2-AG, non-CB(1), probably CB(2)-like receptors are also involved. 相似文献
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化学修饰对金顶侧耳多糖抗病毒(CB5)活性的影响 总被引:12,自引:0,他引:12
从金侧耳子实体中分离纯化一半乳甘露聚糖PC-3,其分子量约为67KD,一级结构a(1→6)糖苷键相连的Gal构成分子的主链,部份残基C2上带有分支,分支结构为a(1-2)Man-a(1-2)Man。按高碘酸氧化、部份酸水解、甲基化、硫酸程序对PC-3的结构进行化学修饰;并分别将PC-3及其衍生物与柯萨厅病毒B5进行体外实验,结果表明,PC-3经硫酸化后,显著地提高了抗病毒活性;而高碘酸氧化,甲基化 相似文献
13.
Cannabinoid CB1 receptor (CB1R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with 13C NMR isotopomer analysis whether CB1Rs could have a local metabolic role in brain areas having high CB1R density, such as the hippocampus. We labelled hippocampal slices with the tracers [2-13C]acetate, which is oxidized in glial cells, and [U-13C]glucose, which is metabolized both in glia and neurons, to evaluate metabolic compartmentation between glia and neurons. The synthetic CB1R agonist WIN55212-2 (1 μM) significantly decreased the metabolism of both [2-13C]acetate (−11.6 ± 2.0%) and [U-13C]glucose (−11.2 ± 3.4%) in the tricarboxylic acid cycle that contributes to the glutamate pool. WIN55212-2 also significantly decreased the metabolism of [U-13C]glucose (−11.7 ± 4.0%) but not that of [2-13C]acetate contributing to the pool of GABA. These effects of WIN55212-2 were prevented by the CB1R antagonist AM251 (500 nM). These results thus suggest that CB1Rs might be present also in hippocampal astrocytes besides their well-known neuronal localization. Indeed, confocal microscopy analysis revealed the presence of specific CB1R immunoreactivity in astrocytes and pericytes throughout the hippocampus.In conclusion, CB1Rs are able to control hippocampal intermediary metabolism in both neuronal and glial compartments, which suggests new alternative mechanisms by which CB1Rs control cell physiology and afford neuroprotection. 相似文献
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Rhizobium、Bradyrhizobium和Azorhizobium能侵染豆科植物并形成根瘤。在根瘤形成过程中,共生伙伴之间首先进行信号物质交换,植物分泌类黄酮(flavonoids)到根际,类黄酮与NodD蛋白结合,进而在转录水平调节其它nod基因的表达,这些nod基因的产物(Nod蛋白)控制根瘤菌产生胞外信号物质(lipochitinoligosaccharide,简称LCO)[1]。LCO能引起宿主植物根毛变形、皮层细胞分裂、根瘤原基及根瘤的形成,因此LCO定名为结瘤因子(nodfa… 相似文献
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Increasing interest has recently been attracted towards the identification of natural compounds including those with antidepressant
properties. Curcumin has shown promising antidepressant effect, however, its molecular target(s) have not been well defined.
Based on the interaction between the neurotrophins and endocannabinoid system as well as their contribution to the emotional
reactivity and antidepressant action, here we show that 4-week treatment with curcumin, similar to the classical antidepressant
amitriptyline, results in the sustained elevation of brain nerve growth factor (NGF) and endocannabinoids in dose-dependent
and brain region-specific fashion. Pretreatment with cannabinoid CB1 receptor neutral antagonist AM4113, but not the CB2 antagonist SR144528, prevents the enhancement of brain NGF contents. AM4113 exerts no effect by itself. Our findings by presenting
the CB1 receptor-mediated endocannabinoid signaling and NGF as novel targets for curcumin, suggest that more attention should be
focused on the therapeutic potential of herbal medicines including curcumin. 相似文献
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用白内障诱发剂三硝基甲苯、平阳霉素、亚硒酸钠和半乳糖分别加入大鼠晶状体培养基中,共同培养24h,同时在各培养基中分别加入中药合剂CB,以观察其药效,用维生素C作对照。结果表明中药合剂CB能够保护非蛋白质巯基免致氧化,抑制蛋白质巯基交联,降低晶状体不溶性蛋白质中二硫键含量,故中药合剂CB有可能作为抗白内障药物应用于临床。 相似文献
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采用RT-PCR获得黄瓜花叶病毒CMV-CB7株系全长基因组cDNA,经克隆测序发现该CMV的RNA1、2和3分别为3356nt、3045nt和2218nt(序列登录号为:EF216866、DQ785470和EF216867).CMV-CB7基因组cDNA克隆体外转录RNA接种心叶烟引起坏死症状,而CMV-Fny则产生典型花叶.由CMV-CB7和CMV-Fny基因组RNA相互交换而构建6个假重组型病毒(C1C2F3、C1F2C3、F1C2C3、F1F2C3、F1C2F3和C1F2C3)活性分析表明:CMV-CB7基因组RNA2决定其在寄主上的症状反应.嵌合型RNA2(RNA2F5C3和RNA2C3F5)的寄主侵染活性测定表明:2b基因或RNA23′端非编码序列决定CMV-CB7在心叶烟坏死症状.RNA印迹分析结果显示:CMV-CB7和CMV-FnyF5C3引起寄主坏死与基因组RNA积累没有直接关系. 相似文献