Discovery of a small molecule that inhibits the interaction of anthrax edema factor with its cellular activator, calmodulin

The catalytic efficiency of adenylyl cyclase activity of edema factor (EF) from Bacillus anthracis is enhanced by approximately 1000-fold upon its binding to mammalian protein calmodulin (CaM). A tandem cell-based and protein binding-based screen of a 10,000 member library identified a molecule that inhibits the EF-CaM interaction and therefore the adenylyl cyclase activity. A combination of fluorescence spectroscopy and photolabeling studies showed that the molecule targets the CaM binding region of EF. A series of related compounds were synthesized and evaluated to identify one compound, 4-[4-(4-nitrophenyl)-thiazolylamino]-benzenesulfonamide, that maintained activity against EF but showed minimal toxicity to two cultured cell lines. This compound represents an important reagent to study the role of EF in anthrax pathology and may represent a drug lead against anthrax infection.     

三甲氧基苄啶分子印迹整体柱的制备及色谱性能

选择甲基丙烯酸为功能单体\, 甲基丙烯酸乙二醇双酯为交联剂, 制备了三甲氧基苄啶分子印迹整体柱, 对整体柱材料的形貌进行了表征, 并且研究了TMP和5种磺胺类药物在分子印迹整体柱上的色谱行为.     

PHOTOSENSORY TRANSDUCTION IN CILIATES. II. POSSIBLE ROLE OF G-PROTEIN AND cGMP IN Stentor coeruleus

Abstract— The heterotrichous ciliate, Stentor coerulus , exhibits a welll defines photophobic response to a sudden increase in the intensity of visible light. the phobic reactions usually appear with a latency perios (i.e. a time delay between the onset of the stimulus and the stop response). This latency of phobic response was significatly increased when the cells werw incubated with 8-bromo-guanosine3',5'-cyclic monophospjhate. In the presence of this nucleotide, a reduction of cell responsiveness (i.e. the number of photophobically responding cells) was also observed. similar effects were observed when cells were treated with pertussis toxin, a G-protein activity modulator, and 3'-isobutyl-methylxanthine, an inhibitor of guanosine 3', 5'-cyclic monophosphate (cGMP) phosphodiesterase. the G-protein activator fluoroaluminate and 6-anilino-5,8-quinolinedione (LY 83583) (an effective agent for lowerin cellular cGMP levels) showed opposite effects on hte cell photophobic response. These result indirectly suggesnt that the level of cytoplamic cGMP, possibly modulated by a G-protein-coupled CGMP phosphodiesterase, plays a phototreasducing role in Stentor . In addition, using an antiserum raised against bovine transducin, a cross reacting protein with an apparent molecular mass of 39 kDa was detected on immunoblots. The α-subunits of a Stentor G-protein has also been partially cloned and sequenced. However, the possible coupling between the G-protein and the putative phosphodiesterase remains to be established.     

Studies on Thermodynamics Features of the Interaction between Imidacloprid and Bovine Serum Albumin

At different temperatures, the interactions between imidacloprid （IMI） and bovine serum albumin （BSA） were investigated with a fluorescence quenching spectrum, a synchronous fluorescence spectrum, a three-dimensional fluorescence spectrum and an ultraviolet-visible spectrum. The average values of bonding constants （KLB： 3.424 × 10^4 L,mol^-1）, thermodynamic parameters （△H： 5.188 kJ,mol^-1, △G^（○—）：-26.36 kJ,mol^-1, △S： 103.9 J,K^-1,mol^-1） and the numbers of bonding sites （n： 1.156） could be obtained through Stern-Volmer, Lineweaver-Burk and ther- modynamic equations. It was shown that the fluorescence of BSA could be quenched for its reactions with IMI to form a certain kind of new compound. The quenching belonged to a static fluorescence quenching, with a non-radiation energy transfer happening within a single molecule. The thermodynamic parameters agree with △H〉 0, △S〉0 and△G^（○-）〈0, suggesting that the binding power between IMI and BSA should be mainly a hydrophobic interaction.     

Synthesis,structures and properties of two novel copper(II) complexes with hydrogen bonding supramolecular networks

Two novel complexes, [Cu(HL)₂(H₂O)]₂(OH)₂(ClO₄)₂·1.5H₂O (1) and [Cu(HL)₂]Cl₂·4H₂O (2), have been prepared by reacting copper salts with the 4-amino-3-ethyl-1,2,4-triazole-5-thione (HL) ligand in neutral solution and in HCl (6 mol L^–1) medium, respectively. They were characterized by FT-IR and u.v.–vis. spectra, and the structures were determined by single crystal X-ray diffraction techniques. In both complexes, the triazole ligand chelated the metal ions through the amine and thione substituents on the five-membered ring. Complex (1) has a square-pyramidal copper(II) ion coordinated by two triazole ligands and one water molecule. Unlike (1), the Cu²⁺ ion in (2) displays its characteristic Jahn–Teller distortion with the distance of the Cl^– anions to metal ion further away than that of the triazole ligands. The most intriguing structural features of the title complexes are that the HL ligands chelate copper(II) ions through the N(1) and S(1) atoms, in a cis mode in (1) and a trans mode in (2). In both cases, self-assembled crystals, by supramolecular contacts simultaneously, form two multi-dimensional frameworks.     

Thermal Reaction of Azulene and Some of Its Symmetrically Substituted Methyl Derivatives with Dimethyl Acetylenedicarboxylate

It is shown that azulene ( 1 ) and dimethyl acetylenedicarboxylate (ADM) in a fourfold molar excess react at 200° in decalin to yield, beside the known heptalene- ( 5 ) and azulene-1,2-dicarboxylates ( 6 ), in an amount of 1.6% tetramethyl (1RS,2RS,5SR,8RS)-tetracyclo[6.2.2.2^2,50^1,5]tetradeca-3,6,9,11,13-pentaene-3,4,9,10-tetracarboxylate(‘anti’-7) as a result of a SHOMO (azulene)/LUMO(ADM)-controlled addition of ADM to the seven-membered ring of 1 followed by a Diels-Alder reaction of the so formed tricyclic intermediate 16 (cf. Scheme 3) with a second molecule of ADM. The structure of ‘anti’-7 was confirmed by an X-ray diffraction analysis. Similarly, the thermal reaction of 5,7-dimehtylazulene ( 3 ) with excess ADM in decalin at 120° led to the formation of ca. 1% of ‘anti’- 12 , the 7,12-dimethyl derivative of‘anti’-7, beside of the corresponding heptalene- 10 and azulene-1,2-dicaboxylated (cf Scheme 2). The introduction of Me groups at C(1)and C(3)of azulene ( 1 ) and its 5,7-dimethyl derivative 3 strongly enhance the thermal formation of the corresponding tetracyclic compound. Thus, 1,3-dimethylazulene ( 2 ) in the presence of a sevenfold molar excess of ADM at 200° yielded 20% of ‘anti’- 9 beside an equal amount of dimethyl 3-mehtylazulene-1,2-dicarboxylate ( 8 ;cf. Scheme 1), and 1,3,5,7-tetramethylazulene ( 4 ) with a fourfold molar excess of ADM AT 200° gave a yield of 37% of‘anti’- 15 beside small amount of the corresponding heptalene- 13 and azulene-1,2-dicarboxylates 14 (cf.Scheme 2).     

Determination of Picogram-Levels of Acetylspiramycin in Human Urine and Serum by Flow Injection Chemiluminescence

A sensitive chemiluminescence method for the determination of acetylspiramycin is presented. It is based on the greatly enhancive effect of acetylspiramycin on the chemiluminescence reaction between luminol and hydrogen peroxide in the flow system. The increase in chemiluminescence intensity was linearly proportional to the acetylspiramycin concentration in the range from 10pg·mL^–1 to 2.0ng·mL^–1 (r²=0.9979). The detection limit was 3pg·mL^–1 (3). At a flow rate of 2.0mL·min^–1, the process of determination, including sampling and washing, could be performed in 0.5 min, and the relative standard deviations of seven replicates are less than 5.0%. The proposed method was applied successfully to the determination of acetylspiramycin in pharmaceutical preparations, human urine and serum without pre-treatment. It was found that the excretive ratio of acetylspiramycin reached its maximum 2.0 hours after having been administered orally, and the excretive ratio in 12.0 hours was 8.4.     

Gold nanoparticles: catalyst for the oxidation of NADH to NAD(+)

Nicotinamide adenine dinucleotide is an important coenzyme involved in the production of ATP, the fuel of energy, in every cell. It alternates between the oxidized form NAD(+) and the reduced form dihydronicotinamide adenine dinucleotide (NADH) and serves as a hydrogen and electron carrier in the cellular respiratory processes. In the present work, the catalytic effect of gold nanoparticles on the oxidization of NADH to NAD(+) was investigated. The addition of gold nanoparticles was found to quench the NADH fluorescence intensities but had no effect on the fluorescence lifetime. This suggested that the fluorescence quenching was not due to coupling with the excited state, but due to changing the ground state of NADH. The intensity of the 340 nm absorption band of NADH was found to decrease while that of the 260 nm band of NAD(+) was found to increase as the concentration of gold nanoparticles increased. This conversion reaction was further supported by nuclear magnetic resonance and mass spectroscopy. The effect of the addition of NADH was found to slightly red shift and increase the intensity of the surface plasmon absorption band of gold nanoparticles at 520 nm. This gives a strong support that the conversion of NADH to NAD(+) is occurring on the surface of the gold nanoparticles, i.e. NADH is surface catalyzed by the gold nanoparticles. The catalytic property of this important reaction might have important future applications in biological and medical fields.     

DFT studies on the multi‐channel reaction of CH3S+NO2

The mechanisms for the reaction of CH₃S with NO₂ are investigated at the QCISD(T)/6‐311++G(d,p)//B3LYP/6‐311++G(d,p) on both single and triple potential energy surfaces (PESs). The geometries, vibrational frequencies, and zero‐point energy (ZPE) correction of all stationary points involved in the title reaction are calculated at the B3LYP/6‐311++G(d,p) level. More accurate energies are obtained at the QCISD(T)/6‐311++G(d,p). The results show that 5 intermediates and 14 transition states are found. The reaction is more predominant on the single PES, while it is negligible on the triple PES. Without any barrier height for the whole process, the main channel of the reaction is to form CH₃SONO and then dissociate to CH₃SO+NO. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Co3{CH3C(NH3)(PO3H)(PO3)}2 {CH3C(NH3)(PO3H)2}2(H2O)4·2H2O: A cobalt 1-aminoethylidenediphosphonate with a layer structure

This paper describes the structure and magnetic properties of a novel cobalt 1-aminoethylidenediphosphonate compound, namely Co₃{CH₃C(NH₃)(PO₃H)(PO₃)}₂{CH₃C(NH₃)(PO₃H)₂}₂(H₂O)₄·2H₂O (1). The structure contains a trimer unit of Co₃{CH₃C(NH₃)(PO₃H)(PO₃)}₂ in which two equivalent phosphonate ligands chelate and bridge the three cobalt ions. Each trimer unit is further linked to its four equivalent neighbors through corner-sharing of CoO₆ octahedra and CPO₃ tetrahedra, forming a two-dimensional layer in the bc-plane which contains 12-membered rings. These layers are connected to each other by extensive hydrogen bonds. Magnetic studies show that weak antiferromagnetic interactions are mediated between the cobalt ions. Crystal data for 1: monoclinic, space group C2/c, a=27.727(4), b=7.1091(11), , β=118.488(3), , Z=2.