Inhibition of galectins with small molecules

Evidence that the galectin family of proteins plays crucial roles in cancer, inflammation, and immunity has accumulated over the last decade. The galectins have consequently emerged as interesting drug targets. A majority of galectin functions occurs by means of cross-linking glycoproteins and by doing so controlling glycoprotein cellular localization and residence times. The glycoprotein cross-linking occurs when galectin dimers or multimers, or galectins with two binding sites, bind galactose-containing glycans of the glycoproteins. Such galectin-glycan interactions have been successfully blocked with compounds having multivalent presentation of galactose, lactose, or N-acetyllactosamine, with peptides, and with small carbohydrate (galactose) derivatives. This review summarizes and analyzes attempts to develop efficient and selective small-molecule galectin inhibitors through derivatization of monosaccharides, mainly galactosides, with non-carbohydrate structures that protrude into subsites adjacent to the core-conserved galactose-recognizing site of the galectins.     

Enzymatic hydrogelation of small molecules

Enzymes, a class of highly efficient and specific catalysts in Nature, dictate a myriad of reactions that constitute various cascades in biological systems. Self-assembly, a process prevalent in Nature, also plays important roles in biology, from maintaining the integrity of cells to performing cellular functions and inducing abnormalities that cause disease. To explore enzyme-regulated molecular self-assembly in an aqueous medium will help to understand and control those important biological processes. On the other hand, certain small organic molecules self-assemble in water to form molecular nanofibers and result in a hydrogel, which is referred to as a "supramolecular hydrogel" (and the small molecules are referred to as "supramolecular hydrogelators"). Supramolecular hydrogelators share common features, such as amphiphilicity and supramolecular interactions (pi-pi interactions, hydrogen bonding, and charge interactions among the molecules, among others) that result in nanostructures and form the three-dimensional networks as the matrices of hydrogels. In this Account, we discuss the use of enzymes to trigger and control the self-assembly of small molecules for hydrogelation, which takes place in vitro or in vivo, extra- or intracellularly. Using phosphatase, thermolysin, beta-lactamase, and phosphatase/kinase as examples, we illustrate the design and application of enzyme-catalyzed or -regulated formation of supramolecular hydrogels that offer a new strategy for detecting the activity of enzymes, screening for enzyme inhibitors, typing bacteria, drug delivery systems, and controlling the fate of cells. Since the expression and distribution of enzymes differ by the types and states of cells, tissues, and organs, using an enzymatic reaction to convert precursors into hydrogelators that self-assemble into nanofibers as the matrices of the hydrogel, one can control the delivery, function, and response of a hydrogel according to a specific biological condition or environment, thus providing an accessible route to create sophisticated materials for biomedicine. Particularly, intracellular enzymatic hydrogelation of small molecules offers a unique means for scientists to integrate molecular self-assembly with inherent enzymatic reactions inside cells for developing new biomaterials and therapeutics at the supramolecular level and improving the basic understanding of dynamic molecular self-assembly in water.     

Reactions of small covalent molecules with coal: trifluoroacetic acid

Anhydrous ammonia, methanol, and other protonic reagents have been utilized for the chemical comminution of coal. In this investigation, subbituminous, low-volatile bituminous and high-volatile bituminouscoals have been comminuted readily by trifluoroacetic acid. Approximately 5% of the original coal dissolves during the trifluoroacetic acid treatment leaving a material which has a high calorific value. The pyritic and organic sulphur contents and the ash yields are greatly reduced. Micrographs after treatment show the layered structure of the coal.     

有机小分子与DNA的相互作用及其在DNA分析中的应用

以有机小分子与DNA的作用机理为基础，从分光光度法、荧光法、光散射技术、电化学分析方法等多种分析手段出发，详细阐述了有机试剂在DNA分析中的最新应用进展，并对今后的发展趋势进行了展望。     

蛋白质与有机小分子反应机理的研究

评述了有机小分子与蛋白质的相互作用机理的研究结果和研究方法。     

Polymer degradation by elimination of small molecules

An outline of a method of deriving the kinetic equations for polymer degradation by the elimination of low molecular weight compounds is presented. The method is based on the stochastic approach. The main ideas are that the degradation occurs via the zip mechanism and that the initiating step, i.e. the formation of an olefinic site in the polymer chain, takes place at random. Three mechanisms have been investigated in this study: (i) ordinary zip mechanism; (ii) autocatalytic mechanism with immediate zip growth and catalyzed initiation; (iii) autocatalytic mechanism with gradual zip growth. The kinetic equations derived have been used in kinetic studies of the dehydrochlorination of PVC in inert, HCl, and oxidative atmospheres, and of the degradation of polyvinyl esters, polyvinyl bromide and polyvinylidene chloride. Kinetic parameters for the degradation of individual polymers have been obtained.     

Assessing the differential affinity of small molecules for noncanonical DNA structures

The targeting of higher-order DNA structures has been thoroughly developed with G-quadruplex DNA but not with other structures like branched DNA (also known as DNA junctions). Because these alternative higher-order DNA architectures might be of high biological relevance, we implemented a high-throughput version of the FRET melting assay that enabled us to map the interactions of a candidate with four different DNA structures (duplex- and quadruplex DNA, three- and four-way junctions) in a rapid and reliable manner. We also introduce a novel index, the BONDS (branched and other noncanonical DNA selectivity) index, to conveniently quantify this differential affinity.     

Achieving regio- and enantioselectivity of P450-catalyzed oxidative CH activation of small functionalized molecules by structure-guided directed evolution

Directed evolution of the monooxygenase P450-BM3 utilizing iterative saturation mutagenesis at and near the binding site enables a high degree of both regio- and enantioselectivity in the oxidative hydroxylation of cyclohexene-1-carboxylic acid methyl ester. Wild-type P450-BM3 is 84% regioselective for the allylic 3-position with 34% enantioselectivity in favor of the R alcohol. Mutants enabling R selectivity (>95% ee) or S selectivity (>95% ee) were evolved, while reducing other oxidation products and thus maximizing regioselectivity to >93%. Control of the substrate-to-enzyme ratio is necessary for obtaining optimal and reproducible enantioselectivities, an observation which is important in future protein engineering of these mono-oxygenases. An E. coli strain capable of NADPH regeneration was also engineered, simplifying directed evolution of P450 enzymes in general. These synthetic results set the stage for subsequent stereoselective and stereospecific chemical transformations to form more complex compounds, thereby illustrating the viability of combining genetically altered enzymes as catalysts in organic chemistry with traditional chemical methods.     

电感耦合等离子体原子发射光谱法测定铝合金中14种元素

铝合金经过处理后,采用电感耦合等离子体原子发射光谱法(ICP-AES)测定铝合金中铅、镉、铬、砷、铜、镍、锌、钾、锶、钡、锰、钴、钼、硒14种元素的含量。对仪器的工作条件进行了优化,选择各元素的分析线,测定各元素的检出限。对铝合金样品进行分析,14种元素测定的相对标准偏差RSD(n=9)在0.061%～6.3%之间。     

Diffusion phenomena of small molecules in polyelectrolyte solutions

Summary From diffusion data of xylose in poly (acrylic acid) and in poly(sodium acrylate) aqueous solutions, the behaviour of these polymers in solution is discussed. When these polyelectrolytes are ionized and expanded in water, consequently, the diffusion phenomena of xylose in these solutions follows the theory of linear macromolecules in solution. When NaCl is added in poly (acrylic acid) solution, the polymer chain contracts and becomes spherical. Therefore, xylose cannot pass through the polymer domain. With poly(sodium acrylate), however, an effect of salt has not been found. Furthermore, effects of neutralization are discussed.     

Solubility and diffusion of small molecules in PVC

Recent studies have shown that the amount and rate of absorption of gases and organic liquids and vapors in rigid and plasticized PVC can be correlated with their molecular dimensions, solvent power, and thermodynamic activity. The amount absorbed at equilibrium depends upon the solvent power of the diffusant, expressed in the Flory-Huggins interaction parameter, x, and upon the vapor pressure or activity of the diffusant in the environment of the PVC. The rate and kinetic form of the approach to equilibrium vary with the ratio of the final uptake to C_g, the diffusant concentration which produces the glass-rubber transition at the experimental temperature. At concentrations far below C_g, absorption follows ideal Fickian kinetics with diffusion coefficients steeply dependent upon the diffusant molecular size and shape. When the concentration approaches or exceeds C_g, absorption is faster, kinetics are non-Fickian, and the dependence upon molecular size is diminished. Carbon dioxide at high pressure strongly accelerates the absorption of other substances because it uniquely combines the high diffusivity of a small gas molecule with the solubility and plasticizing action of an organic swelling agent.     

Diamond nanowires for highly sensitive matrix-free mass spectrometry analysis of small molecules

This paper reports on the use of boron-doped diamond nanowires (BDD NWs) as an inorganic substrate for matrix-free laser desorption/ionization mass spectrometry (LDI-MS) analysis of small molecules. The diamond nanowires are prepared by reactive ion etching (RIE) with oxygen plasma of highly boron-doped (the boron level is 10(19) B cm(-3)) or undoped nanocrystalline diamond substrates. The resulting diamond nanowires are coated with a thin silicon oxide layer that confers a superhydrophilic character to the surface. To minimize droplet spreading, the nanowires were chemically functionalized with octadecyltrichlorosilane (OTS) and then UV/ozone treated to reach a final water contact angle of 120°. The sub-bandgap absorption under UV laser irradiation and the heat confinement inside the nanowires allowed desorption/ionization, most likely via a thermal mechanism, and mass spectrometry analysis of small molecules. A detection limit of 200 zeptomole for verapamil was demonstrated.     

Cyclodextrin-based low molecular weight polymers as encapsulates for nonpolar drug molecules

A quaternized ammonium photoinitiator was synthesized via Michael-addition reaction and quaternization reaction, then ion-exchanged with montmorillonite (MMT). An ordered swollen structure of the intercalated montmorillonite was confirmed by X-ray powder diffraction (XRD) and thermogravimetric analysis (TGA). UV–vis absorption spectroscopy was employed to investigate the maximal absorption of photoinitiator and the intercalated montmorillonite. The modified montmorillonite was then mixed with urethane acylate oligomer (CN964) and tripropylene glycol diacrylate (TPGDA) to form Polyurethane/montmorillonite nanocomposites by photopolymerization. The photopolymerization kinetics was monitored by real time infrared spectroscopy (RTIR). The X-ray diffraction and transmission electron microscopy (TEM) results revealed that the modified montmorillonite was exfoliated and dispersed in parallel alignments as multilayers in the organic matrix.     

First-principles molecular dynamics study of small molecules in zeolites

We present first-principles (based on electronic structure calculations) molecular dynamics simulations of the adsorption of methanol and water in zeolites. In contrast to most previous calculations we take the infinite zeolite structure fully into account. Our calculations reproduce the measured IR spectra, and thus allow for the first time a direct assignment of the measured bands. Methanol and water appear not to be protonated at low (one molecule per acid site) coverages. At higher coverages, however, the proton detaches from the framework and is available for acid catalyzed reactions in the zeolite. We precede our discussion with a critical evaluation of available theoretical approaches.     

Transport of small molecules through mechanically elongated polymeric membranes

This contribution presents an analysis of the problem of diffusion through membranes, incorporating a realistic downstream boundary condition. The analysis can be applied to operations involving geomembranes. Graphs are presented to show the effect of the various dimensionless parameters. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1200–1203, 2005