The β-Carboline Analog Mana-Hox Causes Mitotic Aberration by Interacting with DNA

Mana-Hox, an analog of beta-carbolines with anticancer activity, induces aberrant mitosis and delays mitotic exit. However, the cellular target is not known. In this study, we visualized the intracellular localization of Mana-Hox. Mana-Hox rapidly penetrated into cells (within 1 min) and concentrated on disorganized metaphase chromosomes after 13 hr of exposure. We demonstrated that Mana-Hox is a noncovalent DNA binder that can interact with DNA through intercalation and/or through minor groove binding. Furthermore, Mana-Hox also inhibits topoisomerase II relaxation activity in vitro, suggesting that Mana-Hox could perturb mitotic chromosome decatenation. Overall, Mana-Hox binding to DNA plays a critical role in the induction of aberrant mitosis and contributes to its anticancer activity.     

Morphological characterization of amidinophenylporphyrins interacting with DNA by photo irradiation

5,10,15,20-Tetrakis（4-amidinophenyl）porphyrin（Por 1）,its Zn complex（Por 2）and amidinophenyl bispophyrin（Por 3）interacting with calf thymus DNA were investigated by scanning electron microscopy（SEM）and the shape and size of the porphyrin–DNA complexes were observed after photo irradiation.The results showed that the shape and size of DNA had signifcant differences with blank group by virtue of the interaction between the porphyrins and ct-DNA.This suggests the morphological characterization could be used to study the interaction and judge DNA photocleavage activity indirectly through the photo irradiation of porphyrins.     

Photochemical DNA cleavage by a Berenil analog

Berenil [bis(4-amidinophenyl)1,3-triazene] is a photostable DNA-binding ligand. We describe here the synthesis of N-(3-hydroxypropyl)-Berenil, which in contrast to Berenil is photosensitive to 360 nm irradiation, behaving as a caged diazonium salt. The 4-amidinobenzenediazonium fragment produced by photolysis induces DNA modification and cleavage.     

Electrochemical studies of quercetin interacting with DNA

An electrochemical investigation of the interaction between quercetin and DNA is reported for the first time. When DNA was added into quercetin solution, both the reduction and oxidation currents of quercetin decreased with few changes in the peak potentials. There was no great difference between the electrochemical parameters determined from the native quercetin solution and those from the solution mixed with DNA. We assume that quercetin interacting with DNA produces an electrochemically inactive supramolecular complex via intercalation. Comparing the phenomena motioned above with those of interaction between morin and DNA, we infer the possible active part of quercetin that interacts with DNA.     

Voltammetric and spectroscopic investigations of 4-nitrophenylferrocene interacting with DNA

Cyclic voltammetry (CV) coupled with UV–vis and fluorescence spectroscopy were used to probe the interaction of potential anticancer drug, 4-nitrophenylferrocene (NFC) with DNA. The electrostatic interaction of the positively charged NFC with the anionic phosphate of DNA was evidenced by the findings like negative formal potential shift in CV, ionic strength effect, smaller bathochromic shift in UV–vis spectroscopy, incomplete quenching in the emission spectra and decrease in viscosity. The diffusion coefficients of the free and DNA bound forms of the drug were evaluated from Randles–Sevcik equation. The binding parameters like binding constant, ratio of binding constants (K_red/K_ox), binding site size and binding free energy were determined from voltammetric data. The binding constant was also determined from UV–vis and fluorescence spectroscopy with a value quite close to that obtained from CV.     

α- 噻吩甲酰三氟丙酮-哌啶铈对DNA和磷酸二酯键模型物(BDNPP)的作用研究

稀土金属的β-二酮类配合物已经成为重要的发光材料、生物组织探针和核磁位移试剂[1],由于它既有一定的理论意义又有较大的实用价值,引起了人们的极大兴趣[2-4].最近几年,过渡金属化合物在发展DNA分子探针和化学疗法领域已经变得非常重要[5]. 我们知道,镧系离子拥有独一无二的电子特征,即:长荧光寿命,强的发射带,配合物的吸收和发射带之间存在有巨大的能差[6].     

Determination of beta-carboline alkaloids in foods and beverages by high-performance liquid chromatography with electrochemical detection at a glassy carbon electrode modified with carbon nanotubes

Simple and sensitive methods for the separation and quantification of β-carboline alkaloids in foods and beverages by HPLC with electrochemical detection at carbon nanotubes-modified glassy carbon electrodes (CNTs-GCE) are reported. Electrode modification with multi-wall CNTs produced an improved amperometric response to β-carbolines, in spite of the working medium consisting of methanol:acetonitrile: 0.05 mol L⁻¹ Na₂HPO₄ solution of pH 9.0 (20:20:60). On the contrary to that observed at a bare GCE, a good repeatability of the amperometric measurements carried out at +900 mV versus Ag/AgCl (R.S.D. of 3.2% for i_p, n = 20) was achieved at the CNTs-GCE. Using an Ultrabase C₁₈ column and isocratic elution with the above mentioned mobile phase, a complete resolution of the chromatographic peaks for harmalol, harmaline, norharmane, harmane and harmine, was achieved. Calibration graphs over the 0.25-100 μM range with detection limits ranging between 4 and 19 ng mL⁻¹, were obtained. The HPLC-ED at CNTs-GCE method was applied to the analysis of beer, coffee and cheese samples, spiked with β-carbolines at concentration levels corresponding to those may be found in the respective samples. The steps involved in sample treatment, such as extraction and clean-up, were optimized for each type of sample. Recoveries ranging between 92 and 102% for beer, 92 and 101% for coffee, and 88 and 100% for cheese, at sub-μg mL⁻¹ or g⁻¹ analytes concentration levels were achieved.     

Abnormally high heat generation by transition metals interacting with hydrogen and oxygen molecules

Abnormally high heats, exceeding 2000 kJ/mol (20 eV) per molecule of O₂, are generated by interaction of the oxygen with the hydrogen absorbed on palladium, gold and nickel particles at 25 °C to 220 °C. The highest heats were observed when the metals were treated with micromole quantities of argon, prior to absorption of hydrogen, as well as its interactions with metal particles reaching nanometer size. In the latter case the heat evolutions due to the interactions with hydrogen were approaching 5000 kJ/mol. The interactions with oxygen in inert gas environments, such as that of argon, yielded higher heat evolutions than those given by pure O₂ pulses injected into nitrogen carrier gas. The results revealed an important role of argon in increasing the intensity of atomic hydrogen-oxygen reactions to a level several times higher than the heat of water formation from molecular hydrogen and oxygen.     

尼古丁与DNA相互作用的电化学研究

用线性扫描伏安法、循环伏安法及光谱法研究了尼古丁与DNA在0.2 mol/LpH 6.0的H2C2O4缓冲溶液中的相互作用。研究结果显示,随着DNA的加入,尼古丁峰电流降低,峰电位正移,说明尼古丁是以嵌入形式与DNA结合,生成了一种结合比为2∶1的非电活性化合物,结合常数β为1.56×109。并用多种电化学方法求得了电极过程的动力学参数。     

Identification of proteins interacting with ammodytoxins in Vipera ammodytes ammodytes venom by immuno-affinity chromatography

In order to perform their function, proteins frequently interact with other proteins. Various methods are used to reveal protein interacting partners, and affinity chromatography is one of them. Snake venom is composed mostly of proteins, and various protein complexes in the venom have been found to exhibit higher toxicity levels than respective components separately. Complexes can modulate envenomation activity of a venom and/or potentiate its effect. Our previous data indicate that the most toxic components of the Vipera ammodytes ammodytes (Vaa) venom isolated so far—ammodytoxins (Atxs)—are contributing to the venom’s toxicity only moderately; therefore, we aimed to explore whether they have some interacting partner(s) potentiating toxicity. For screening of possible interactions, immuno-affinity chromatography combined with identification by mass spectrometry was used. Various chemistries (epoxy, carbonyldiimidazole, ethylenediamine) as well as protein G functionality were used to immobilize antibodies on monolith support, a Convective Interaction Media disk. Monoliths have been demonstrated to better suit the separation of large biomolecules. Using such approach, several proteins were indicated as potential Atx-binding proteins. Among these, the interaction of Atxs with a Kunitz-type inhibitor was confirmed by far-Western dot-blot and surface plasmon resonance measurement. It can be concluded that affinity chromatography on monolithic columns combined with mass spectrometry identification is a successful approach for screening of protein interactions and it resulted with detection of the interaction of Atx with Kunitz-type inhibitor in Vaa venom for the first time.     

The Xe shielding surfaces for Xe interacting with linear molecules and spherical tops

The 129Xe nuclear magnetic resonance spectrum of xenon in gas mixtures of Xe with other molecules provides a test of the ab initio surfaces for the intermolecular shielding of Xe in the presence of the other molecule. We examine the electron correlation contributions to the Xe-CO2, Xe-N2, Xe-CO, Xe-CH4, and Xe-CF4 shielding surfaces and test the calculations against the experimental temperature dependence of the density coefficients of the Xe chemical shift in the gas mixtures at infinite dilution in Xe. Comparisons with the gas phase data permit the refinement of site-site potential functions for Xe-N2, Xe-CO, and Xe-CF4 especially for atom-Xe distances in the range 3.5-6 A. With the atom-atom shielding surfaces and potential parameters obtained in the present work, construction of shielding surfaces and potentials for applications such as molecular dynamics averaging of Xe chemical shifts in liquid solvents containing CH3, CH2, CF3, and CF2 groups is possible.     

Pim1 promotes IFN-β production by interacting with IRF3

The Pim (proviral integration site for Moloney murine leukemia virus) proteins compose a serine threonine kinase family whose members regulate cell proliferation, migration and cell survival. However, whether Pim kinases participate in innate immune responses is unclear. Here, we show for the first time that Pim1 plays an essential role in the production of interferon (IFN)-β by macrophages after their Toll-like receptor (TLR) pathway is activated by pathogen-associated molecular patterns (PAMPs). Specifically, Pim1 was quickly upregulated in an NF-κB-dependent manner after TLR stimulation with PAMPs. Pim1 deficiency reduced TLR3- or TLR4-stimulated IFN-β and IFN-stimulated gene (ISG) expression but not proinflammatory cytokine expression in macrophages. Mechanistically, Pim1 specifically upregulates IRF3 phosphorylation and nuclear translocation. However, this role is not dependent on Pim1 kinase activity. Rather, Pim1 appears to promote IRF3 phosphorylation by enhancing the formation of IFN-β signaling complexes composed of TRIF, TRAF3, TBK1, and IRF3. Poly (I:C)-treated Pim1^−/− mice produced less serum IFN-β and were less likely to survive than wild-type mice. These findings show for the first time that Pim1 participates in TLR-mediated IFN-β production, thus revealing a novel target for controlling antiviral innate immune responses.Subject terms: Toll-like receptors, Phagocytes     

Recent developments in the characterization of water interacting with proteins by 17O NMR

Transverse and longitudinal ¹⁷O-water relaxation rates were detected in different samples of BSA solutions after one-quantum and triple-quantum-filtered NMR sequences. Another contribution other than quadrupolar relaxation was found for transverse relaxation, which did not change significantly with the concentration and hence could not correspond to agglomeration of proteins. This was interpreted as chemical exchange between different types of ¹⁷O-water in fast motion; probably free water and water weakly bound to the proteins. At lower BSA concentrations, two peaks were detected for water; this was in agreement with this hypothesis. The interactions between BSA and lactic acid were also studied. It was shown that at a sufficient concentration of lactic acid, the number of strongly bound water molecules detected diminishes. On the other hand, the weakly bound water properties do not change significantly.     

The interaction of DNA with dopamine by spectroscopic and electrochemical methods.

It has recently been reported that dopamine may show some biological activities in antitumor and cell apoptosis. We have thoroughly investigated the interaction between dopamine and DNA by CD, UV, fluorescence and electrochemical methods. The results of spectroscopic measurements have indicated that a binding event occurs in a dopamine-DNA system. Besides the electronstatic interaction between a negatively charged DNA molecule and a positively charged dopamine molecule, other binding modes, such as hydrogen-bond and intercalation may also exist in this system. The interaction parameters, including the equilibrium constant and binding numbers, were estimated by an electrochemical method based on the redox current and formal potentials. Both of the two calculation methods showed that the 1:1 type of complex was formed in the dopamine-DNA system and that its equilibrium constant was about 5.85 x 10(6) M(-1). Based on the results of UV, fluorescence and electrochemical experiments in the present study, dopamine may be employed as an effective probe for a DNA assay.     

Improving activity of anticancer oxalipalladium analog by the modification of oxalate group with isopentylglycine

In this article, we describe the influence of structure on biological behavior of amino acid-Pd complex and compare it with oxalipalladium. A new water-soluble oxalipalladium analog with formula of [Pd(DACH)(isopentylgly)](NO₃), where DACH is 1R,2R-diaminocyclohexane, has been synthesized and characterized by elemental analysis, conductivity measurements, IR, UV–Vis, and ¹H NMR spectroscopies. The interactions of oxalipalladium and its amino acid derivative with highly polymerized calf-thymus DNA have been extensively studied by spectroscopic methods. The high binding constants of oxalipalladium (0.38 × 10⁴ M^?1) and new amino acid-Pd complex (0.65 × 10⁴ M^?1) were determined using absorption measurements. Also circular dichroism (CD) studies show that Pd complex causes more disturbances on DNA structure rather than oxalipalladium. The experimental results proposed that [Pd(DACH)(isopentylgly)](NO₃) is bound to DNA by groove-binding mode as well as partially covalent interaction, while oxalate analog binds covalently to DNA after hydrolysis. Interaction of the two metal derivative complexes was studied by molecular docking simulation. The results showed that amino acid-Pd complex has higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line of HCT116 after 24 h incubation time using MTT assay. Results show that the complex [Pd(DACH)(isopentylgly)](NO₃) showed enhanced anticancer and growth inhibitory activities against human colon can cell line HCT116.     

Synthesis and properties of a bilirubin analog with propionic acid groups replaced by carboxyl

The unnatural bile pigment analog of bilirubin-IXα, 2,3,7,13,17,18-hexamethyl-(10H,21H,23H,24H)-bilin-1,19-dione-8,12-dicarboxylic acid (1), was synthesized as its diethyl ester by coupling 4,4′-dimethyl-3,3′-dicarboethoxydipyrrylmethane-5,5′-dialdehyde with 3,4-dimethylpyrrolin-2-one.     

Formation of Pd superoxo complexes by interacting potassium superoxide with palladium acetate in organic solvents

Two types of palladium superoxo complexes resulting from the interaction of potassium superoxide with palladium acetate in organic solvents have been detected by ESR.

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水溶性金属卟啉与DNA相互作用的微量热法研究

叶琳化合物以其对肿瘤组织的特殊亲和性和光动力学效应受到广泛的重视，国内外研究报导甚多·自D79年nel等人山证实水溶性四一K甲基毗陡基）叶咐及其金属配合物能嵌入＊＊A的碱基之间后，人们以这类水溶性叶琳为模型利用各种物理和化学手段研究它们与＊NA相互作用［2，3］．但用微量热法进行研究尚未见报导．我们曾报导用共振拉曼光谱研究图1所示的二个水溶性金属叶琳ru（＊A仰）」和卜i（N＊＊刊I同＊＊A的作用＊‘］，本文进一步报导用微量热法和紫外可见光谱研究的结果．1实验部分1．1试剂将小牛胸腺DN以华美生物工程公司产品）直接…     

DNA damage induced by 4,6,8,9-tetramethyl-2H-furo[2,3-h]quinolin-2-one, a new furocoumarin analog: photochemical mechanisms

Some photochemical and photobiological properties of 4,6,8,9-tetramethyl-2H-furo[2,3-h]quinolin-2-one (HFQ) were studied in comparison with its isomer 1,4,6,8-tetramethyl-2H-furo[2,3-h]quinolin-2-one (FQ) and 8-methoxypsoralen (8-MOP). The HFQ photobinds to DNA forming furan-side monoadducts (MAHFQ) that have molecular structure very similar to those of FQ (MAFQ). Unlike MA8-MOP and MAFQ, MAHFQ no longer photoreact. The HFQ, like FQ, produces moderate amounts of singlet oxygen but no superoxide anions. The HFQ and FQ induce numbers of DNA-protein cross-links (DPC), much more plentiful than those of 8-MOP (about two and seven times, respectively) but no interstrand cross-links. The mechanism of DPC formation was studied in vivo in mammalian cells by alkaline elution and in vitro using a new test mixing histones and DNA from calf thymus. The latter is a very useful technique for the double irradiation protocol. The DNA (or histones) are separately exposed to a first UVA dose in the presence of the sensitizer; then, after its unbound molecules have been removed, histones (or DNA) are added to assemble the chromatin-like complex that is irradiated again. According to in vitro and in vivo methods, DPC appear to be formed by FQ and 8-MOP by a biphotonic process that starts with monoadduct induction in DNA, followed by their conversion into DPC. In the resulting lesions, the sensitizer molecule forms a covalent bridge between the two macromolecules (DPC at length greater than zero). Instead, HFQ induces DPC by a monophotonic process; thus, HFQ is probably not a physical part of the bridge between DNA and proteins, which may be linked together directly, like DPC at zero length induced by UVC.