A structural and energetics analysis of the binding of a series of N-acetylneuraminic-acid-based inhibitors to influenza virus sialidase

Summary A molecular dynamics/energy-minimisation protocol has been used to analyse the structural and energetic effects of functional group substitution on the binding of a series of C4-modified 2-deoxy-2,3-didehydro-N-acetylneuraminic acid inhibitors to influenza virus sialidase. Based on the crystal structure of sialidase, a conformational searching protocol, incorporating multiple randomisation steps in a molecular dynamics simulation was used to generate a range of minimum-energy structures. The calculations were useful for predicting the number, location, and orientation of structural water molecules within protein-ligand complexes. Relative binding energies were calculated for the series of complexes using several empirical molecular modelling approaches. Energies were computed using molecular-mechanics-derived interactions as the sum of pairwise atomic nonbonded energies, and in a more rigorous manner including solvation effects as the change in total electrostatic energy of complexation, using a continuum-electrostatics (CE) approach. The CE approach exhibited the superior correlation with observed affinities. Both methods showed definite trends in observed and calculated binding affinities; in both cases inhibitors with a positively charged C4 substituent formed the tightest binding to the enzyme, as observed experimentally.This paper is based on a presentation given at the 14th Molecular Graphics and Modelling Society Conference, held in Cairns, Australia, August 27–September 1, 1995.Presently on a visiting postdoctoral fellowship in the Department of Biomolecular Structure, Glaxo Research & Development Ltd, Greenford, Middlesex UB6 OHE, U.K.     

制备方法对WO_3/ZrO_2结构的影响

用XRD、比表面测定、LRS定性和定量的方法对用Zr（OH）4和已晶化的ZrO2作载体制得的两类WO3／ZrO2催化剂进行了表征．揭示了样品比表面、载体物相、活性组分的存在状态与制备方法、WO3含量、焙烧温度之间的关系．结果表明，WO3能单层分散在ZrO2上；单层覆盖在Zr（OH）4上的WO3使载体在焙烧时晶粒生长受阻，形成介稳的四方ZrO2，并阻止载体微粒间的烧结，使从Zr（OH）4出发制得的WO3／ZrO2比表面明显增大，在WO3含量达到单层分散容量时以上作用表现得最充分；WO3与Zr（OH）4（或四方ZrO2）在高温（～800℃）可能发生了某种化学结合，开创出超强酸位．用以上观点可对文献中已报导的主要实验事实作出较满意的解释.     

Spin density distributions in radical anions of heterocyclic amine N-oxides

The unrestricted Hartree-Fock (UHF) method of Snyder and Amos is used to calculate, in the -electron approximation, the spin density distributions in radical anions of heterocyclic amine N-oxides. The computed spin densities are observed to be in good agreement with the experimental values. The computed spin density distribution of the radical anion of pyridine N-oxide is consistent with the greater susceptibility of pyridine N-oxide relative to pyridine to electrophilic nitration. Also, the calculations are consistent with the lower basicity of the N-oxides relative to the parent bases.     

The study of terbium generated bacterirhodopsin

The localization of Terbium (Tb³⁺) cations binding to deionized bacteriorhodopsin (bR) has been studied by using spectroscopic methods. It was found that adding Tb³⁺ cations to deionized bR affects the fluorescence lifetimes of tryptophan (Trp) in bR, the wavelength of fluorescence peak shifts “blue” and the peak value of fluorescence decreases. It was also found that adding one Tb³⁺ cation to deionized bR can restore the purple state from its blue state obviously. The measurements of absorbance, fluorescence and lifetime of fluorescence also show that when more than three Tb³⁺ cations are added, no further changes can be found. It is suggested that one Tb³⁺ specific binding site for the color-controlling is located on the exterior of the bR trimer structure to negatively charged lipids near Trp-10 and Trp-12. Three Tb³⁺ cations binding per bR is needed for the regenerated bR.     

Kinetics of no decomposition over Cu/ZSM-5 catalyst

The kinetics of catalytic decomposition of NO over Cu/ZSM-5 catalyst has been studied in an integral flow reactor at atmospheric pressure. Kinetic analysis is based on the assumption that the surface reaction represents the rate-determining step. On the basis of theoretical considerations of different interactions between reactants and catalyst, and experimental evidences, three different mechanistic kinetic models were chosen. Also a power-law model was tested. The best agreement has been achieved with the model

Catalytic phosphorylation of polyfluoroalkanols. 17. Synthesis and the stereochemistry of tris(α-trifluoromethylbenzyl) phosphates

Catalytic phosphorylation of -trifluoromethylbenzyl alcohols with POCl₃ taken in a ratio of 3 : 1 under particular temperature conditions afforded predominantly symmetrical tris(-trifluoromethylbenzyl) phosphates. The latter were obtained as mixtures of two diastereomers with a statistical ratio of the components.     

Metallocene-mediated synthesis of chain-end functionalized polypropylene and application in PP/clay nanocomposites

This paper summarizes our research in the preparation of chain end functionalized isotactic polypropylene (PP) having a terminal functional group, such as Cl, OH, and NH₂. The chemistry involves metallocene-mediated propylene polymerization using rac-Me₂Si[2-Me-4-Ph(Ind)]₂ZrCl₂/MAO complex in the presence of styrene derivatives (St-f) and hydrogen, which serve as the chain transfer agents. The molecular weight of the resulting PP polymers with a terminal Cl, OH and NH₂ group (i.e., PP-t-Cl, PP-t-OH and PP-t-NH₂) are inversely proportional to the molar ratio of [St-f]/[propylene]. Despite the extremely low concentration of functional group, the high molecular weight chain end functionalized PP-t-OH and exhibit a distinctive advantage over other functional PP polymers containing side chain functional groups or long functional blocks. The terminal hydrophilic OH and cations, with good mobility and reactivity, effectively hydrogen bond and ion-exchange the cations (Li⁺, Na⁺, etc.) located between the clay interlayers, respectively. Such interactions anchor the PP chain to the clay surfaces. On the other hand, the remaining rest of the unperturbed end-tethered high molecular weight PP tail exfoliates the clay layers. This exfoliated structure is maintained even after further mixing of the PP-bearing platelets with pure neat PP polymers.     

Solvates of Indomethacin

Indomethacin is known to exhibit polymorphism and solvates, the different forms obtained do not exhibit the same solubility and their bioavailabilities are different. It is of a prime importance to identify the various polymorphic and solvated forms. This study was carried out by: DSC (different scanning calorimetry), TG (thermogravimetric analysis), X-ray diffraction and thermomicroscopy. Seven solvates, with acetone, benzene, dichloromethane, tetrahydrofurane, propanol, chloroform and diethylether, were isolated and studied. Their formulae have been determined by thermogravimetric analysis and their X-ray patterns on powder are presented, by DSC their behaviour after desolvation is recorded, the temperature and the enthalpy of fusion are measured and by this way the form obtained is deduced. This revised version was published online in July 2006 with corrections to the Cover Date.     

Interaction of the mutagen ethidium bromide with DNA, using a carbon paste electrode and a hanging mercury drop electrode

The interaction of ethidium bromide (2,7-diamino-10-ethyl-9-phenylphenanthridinium bromide; EB) with double stranded (ds) calf thymus DNA and thermally denatured single stranded (ss) DNA was studied in solution and at the electrode surface by means of transfer voltammetry using a carbon paste electrode (CPE) as working electrode in 0.2 M acetate buffer, pH 5.0. As a result of intercalation of this dye between the base pairs of dsDNA, the characteristic peak of dsDNA, due to the oxidation of guanine residues, decreased and after a particular concentration of EB a new peak at +0.81 V appeared, probably due to the formation of a complex between dsDNA and EB. The non-intercalated EB gives another peak, but at an increased concentration of the dye. A similar behaviour was observed during the interaction of the dye with ssDNA.Furthermore, the interaction of EB with ds, ss and supercoiled (sc) DNA was studied at the hanging mercury drop electrode (HMDE) surface by means of alternating current voltammetry in 0.3 M NaCl and 50 mM sodium phosphate buffer (pH 8.5) as supporting electrolyte. dsDNA yields a smaller peak at −1.42 V (peak III) compared to the one yielded by ssDNA, since the latter is a relaxed and more accessible form. By addition of EB into the buffer solution an increase of peak III was observed in the dsDNA form as well as in ssDNA resulting from their interaction with EB. Furthermore, the appearance of peak III in covalently closed circular scDNA after exposure to increasing concentrations of EB is a result of the introduction of ‘free ends’ in DNA affecting its structural integrity.     

Studies on the Interaction of Beryllon Ш with Proteins by Voltammetric Technique and its Application

A new quantitative determination method of proteins using beryllon Ш by voltammetric technique was developed in this paper. In pH 3.5 Britton-Robinson (B-R) buffer solution, beryllon Ш can bind with human serum albumin (HSA) to form an electro-inactive supermolecular complex. Beryllon Ш has a well-defined voltammetric reduction peak at -0.38 V (vs. SCE) and the addition of protein in this solution can cause the decrease of the reductive peak current. Based on the decrease of the reduction peak current, a new electrochemical method for the determination of HSA was established with linear range of 1.0~40.0 mg/L and the detection limit of 1.0 mg/L. This method is further applied to the determination of real sample of healthy human serum.