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用微量最热计连续测定细菌代谢过程中的热显变化,可获得反映细菌代谢规律的完整的热谱图以按指数生长模型对指数生长期进行处理,可计算出细菌正常代谢的生长速率常数L’.若在培养基中加入合成药物,使细菌在药物抑制作用下生长,也可获得完整的热谱图,从而计算出在药物抑制作用下细菌的生长速率常数.本义对福氏志贺氏Zb菌和金黄色葡萄球莉在四种合成药物抑制作用下的热谱进行了测定,并计算了生长速率常数,找出了细菌生长速率常数与所用药物浓度之间的定量关系,可为筛选抑菌药物和确定用药显提供定量依据’1基本原理设细菌在代谢过… 相似文献
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由于传统抗生素类药物容易使细菌产生耐药性而成为超级细菌,新型的抗菌药物亟待开发。通过模拟天然抗菌多肽设计合成的高分子抗菌剂,具有很高的抗菌活性和生物选择性,而且由于其合成方法简单,结构易于控制,且可实现大规模工业生产,有望成为代替传统抗生素和抗菌多肽的新一代抗菌药物。本文介绍了天然抗菌多肽的抗菌机理与模拟天然抗菌多肽的... 相似文献
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药物对福氏志贺氏菌代谢抑制的微量热法研究 总被引:11,自引:1,他引:11
药物抑制细菌生长的热化学研究是当今热化学法研究的一个活跃领域.在这项研究中,Boling[1]、Nordmark[2]、屈松生[3]等人已做了不少有意义的工作.在前人工作的基础上,我们用热活性检测系统测定了福氏志贺氏菌属中五株细菌在药物抑制下生长的完整的热谱曲线.按指数生长模型计算出细菌代谢抑制下的生长速车常数,并用计算机拟会出生长速率常数与不同浓度药物之间的关系式,进一步得到生长速率常数为零(临界生长参数[4])时的用药物浓度.此项研究工作的开展对于深入研究药物对细菌的抑制作用,筛选对某细菌抑制的特效药提供了一种新的… 相似文献
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天然铁载体是细菌分泌的一种小分子铁离子螯合剂,与铁离子螯合后可被特定的外膜受体识别并转运至胞浆内为细菌提供必需的铁.利用铁载体分子这种特性,可将药物分子与其偶联,通过细菌铁摄取系统使抗生素进入细菌从而杀死细菌,这一策略被称为"特洛伊木马"策略. 2019年,第一个铁载体-抗生素偶联药物Cefiderocol被批准上市,引起许多专家和制药企业对本领域的研究兴趣.从铁载体分子的类别、不同作用机制的抗生素以及连接体的选择三个方面对铁载体分子偶联抗生素药物进行了较全面的综述,总结了铁载体-抗生素偶联物其三个组成部分分别对于新抗生素发挥抗菌作用的规律,为新型铁载体偶联抗生素药物的研发提供参考. 相似文献
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用微量热法测定了大肠杆菌(细菌)及其在Zn-o-VG(o-VG:邻香草醛氨基葡萄糖Schiff碱)作用下不同温度下的热谱;计算了它的生长速率常数k、传找时间G、抑制率I、总产热量Q、单个细菌的平均产热Q0的单位时间平均每个细菌的产热量^-量Q0;建立了细菌生长代谢各种参量之间的函数关系,探讨了在不同温度和药物作用下细菌的生长代谢;发现可用tg、tr和t表征细菌的生长代谢和药物的抗菌活性。 相似文献
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Schiff碱药物与细菌作用的半抑制量比较研究 总被引:8,自引:0,他引:8
用微量热法测定了金黄色葡萄球菌和产气杆菌分别与十一种Schiff碱药物作用的热谱曲线根据热谱曲线计算了细菌生长的速率常数K,建立了K~C关系式,进行在获得的Schiff碱药物对细菌作用的半抑制量C1/2的基础上,通过对半抑制量大小的比较,分别对配体相同金属离不同,金属离子相同配体不同的Schiff碱药物与细菌的作用以及对同一药物与不同细菌作用的情况做了较深入的讨论,发现,同一药物对不同的菌种其药效 相似文献
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The regioselectivity of the oxidation of three monosubstituted olefins, 6-phenoxyhex-1-ene, hex-1-ene and styrene, by iodosobenzene in the presence of various Fe-, Mn- or Cr-tetraaryl-porphyrins, was studied. It was found that, besides epoxides, known products from such systems, allylic alcohols and aldehydes were formed, the latter not being derived from the corresponding epoxides. The relative importance of these reactions greatly depends upon both the metal and porphyrin constituents of the catalyst. More particularly, the competition between epoxidation and allylic hydroxylation can be efficiently controlled by non-bonded interactions between the olefin and porphyrin substituents. No hydroxylation of the aromatic rings and no oxidative dealkylation of the ether function was detected. 相似文献
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Three chiral compounds were successfully separated in a short time with two enantiomer separation models on packed-capillary electrochromatography (CEC). (i) 75 μm I.D. capillaries were packed with 5 μm β-cyclodextrin (β-CD) chiral stationary phase (CSP). Effects of voltage, pH and concentration of organic modifier on electroosmotic flow (EOF) and chiral separations were investigated systematically. Enantiomers of a neutral compound (benzoin) and a neutral drug (mephenytoin) were separated within a short time with high efficiency. Efficiency of 32 000 theoretical plates per meter and resolution (R_s) of 1.42 were achieved for enantiomers of benzoin using a βCD packed column with 6.2 cm packed length. Efficiency of 45 000 theoretical plates per meter and R_s of 3.40 were obtained for enantiomers of mephenytoin. Especially, the enantiomer separation of mephenytion was performed in just 3.4 min with R_s of 2.60. (ⅱ) 75 μm I.D. capillary was packed with octadecylsilica particles (ODS). Chiral separat 相似文献
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Pata V Ahmed F Discher DE Dant N 《Langmuir : the ACS journal of surfaces and colloids》2004,20(10):3888-3893
The commonly held model for membrane dissolution by detergents/surfactants requires lipid transport from the inner to the outer bilayer leaflet ('flip-flop'). Although applicable to many systems, it fails in cases where cross-bilayer transport of membrane components is suppressed. In this paper we investigate the mechanism for surfactant-induced solubilization of polymeric bilayers. To that end, we examine the dissolution of a series of increasingly thick, polymer-based vesicles (polymersomes) by a nonionic surfactant, Triton X-100, using dynamic light scattering. We find that increasing the bilayer thickness imparts better resistance to dissolution, so that the concentration required for solubilization, after a fixed amount of time, increases nearly linearly with membrane thickness. Combining our experimental data with a theoretical model, we show that the dominant mechanism for the surfactant-induced dissolution of polymeric vesicles, where polymer flip-flop across the membrane is suppressed, is the surfactant transport through the bilayer. This mechanism is different both qualitatively and quantitatively from the mechanisms by which surfactants dissolve pure lipid vesicles. 相似文献
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Spencer J Read J Sessions RB Howell S Blackburn GM Gamblin SJ 《Journal of the American Chemical Society》2005,127(41):14439-14444
Metallo-beta-lactamases are zinc-dependent enzymes responsible for resistance to beta-lactam antibiotics in a variety of host bacteria, usually Gram-negative species that act as opportunist pathogens. They hydrolyze all classes of beta-lactam antibiotics, including carbapenems, and escape the action of available beta-lactamase inhibitors. Efforts to develop effective inhibitors have been hampered by the lack of structural information regarding how these enzymes recognize and turn over beta-lactam substrates. We report here the crystal structure of the Stenotrophomonas maltophilia L1 enzyme in complex with the hydrolysis product of the 7alpha-methoxyoxacephem, moxalactam. The on-enzyme complex is a 3'-exo-methylene species generated by elimination of the 1-methyltetrazolyl-5-thiolate anion from the 3'-methyl group. Moxalactam binding to L1 involves direct interaction of the two active site zinc ions with the beta-lactam amide and C4 carboxylate, groups that are common to all beta-lactam substrates. The 7beta-[(4-hydroxyphenyl)malonyl]-amino substituent makes limited hydrophobic and hydrogen bonding contacts with the active site groove. The mode of binding provides strong evidence that a water molecule situated between the two metal ions is the most likely nucleophile in the hydrolytic reaction. These data suggest a reaction mechanism for metallo-beta-lactamases in which both metal ions contribute to catalysis by activating the bridging water/hydroxide nucleophile, polarizing the substrate amide bond for attack and stabilizing anionic nitrogen intermediates. The structure illustrates how a binuclear zinc site confers upon metallo-beta-lactamases the ability both to recognize and efficiently hydrolyze a wide variety of beta-lactam substrates. 相似文献
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Raj K. Bansal Neelima Gupta Vijaya Kabra Claudia Spindler Konstantin Karaghiosoff Alfred Schmidpeter 《Heteroatom Chemistry》1992,3(4):359-366
Bromine does not add to phosphorus in a 2-phosphaindolizine 1 but substitutes its 1-position. The 1-bromo derivatives 2 are best prepared with Br2/NEt3 or N-bromosuccinimide. Their hydrolysis is remarkable; it involves a debromination of C-1, an oxidation of P and a selective opening of the P/C-3 bond. PCl3 also causes a substitution of the 1-position. The resulting 1-dichlorophosphino derivatives 5 easily undergo a substituent exchange at the exocyclic phosphorus. More 1-phosphino derivatives are formed in the reaction of 1 with phenyl and diazaphospholyl dichlorophosphine. 相似文献
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Alipázaga MV Moreno RG Linares E Medeiros MH Coichev N 《Dalton transactions (Cambridge, England : 2003)》2008,(41):5636-5644
DNA damage was investigated in the presence of sulfite, dissolved oxygen and cobalt(II) complexes with glycylglycylhistidine, glycylhistidyllysine, glycylglycyltyrosylarginine and tetraglycine. These studies indicated that only Co(II) complexed with glycylglycylhistidine (GGH) induced DNA strand breaks at low sulfite concentrations (1-80 microM) via strong oxidants formed in the reaction. In the presence of the other complexes, some damage occurred only in the presence of high sulfite concentrations (0.1-2.0 mM) after incubation for 4 h. In the presence of GGH, Co(II) and dissolved O2, DNA damage must involve a reactive high-valent cobalt complex. The damaging effect was increased by adding S(IV), due to the oxysulfur radicals formed as intermediates in S(IV) autoxidation catalyzed by the complex. SO3 -, HO and H radicals were detected by EPR-spin trapping experiments with DMPO (5,5-dimethyl-1-pyrroline N-oxide). The results indicate that Co(II) binds O2 in the presence of GGH, and leads to the formation of a DMPO-HO adduct without first forming free superoxide or hydroxyl radical, supporting the participation of a reactive high-valent cobalt complex. 相似文献
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Gupta SC Prasad S Kim JH Patchva S Webb LJ Priyadarsini IK Aggarwal BB 《Natural product reports》2011,28(12):1937-1955
Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca(2+) ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto-enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting binding sites, has also been used to further characterize curcumin's binding sites. Furthermore, the ability of curcumin to bind directly to carrier proteins improves its solubility and bioavailability. In this review, we focus on how curcumin directly targets signaling molecules, as well as the different forces that bind the curcumin-protein complex and how this interaction affects the biological properties of proteins. We will also discuss various analogues of curcumin designed to bind selective targets with increased affinity. 相似文献