Ligand-receptor interactions in tethered polymer layers

The binding of small proteins to ligands that are attached to the free ends of polymers tethered to a planar surface is studied using a molecular theory. The effects of changing the intrinsic binding equilibrium constant of the ligand-receptor pair, the polymer surface coverage, the polymer molecular weight, and the protein size are studied. The results are also compared with the case where ligands are directly attached to the surface without a polymer acting as a spacer. We found that within the biological range of binding constants the protein adsorption is enhanced by the presence of the polymer spacers. There is always an optimal surface coverage for which ligand-receptor binding is a maximum. This maximum increases as the binding energy and/or the polymer molecular weight increase. The presence of the maximum is due to the ability of the polymer-bound proteins to form a thick layer by dispersing the ligands in space to optimize binding and minimize lateral repulsions. The fraction of bound receptors is unity for a very small surface coverage of ligands. The very sharp decrease in the fraction of bound ligand-receptor pairs with surface coverage depends on the polymer spacer chain length. We found that the binding of proteins is reduced as the size of the protein increases. The orientation of the bound proteins can be manipulated by proper choice of the grafted layer conditions. At high polymer surface coverage the bound proteins are predominantly perpendicular to the surface, while at low surface coverage there is a more random distribution of orientations. To avoid nonspecific adsorption on the surface, we studied the case where the surface is covered by a mixture of a relatively high molecular weight polymer with a ligand attached to its free end and a low molecular weight polymer without ligand. These systems present a maximum in the binding of proteins, which is of the same magnitude as when only the long polymer-ligand is present. Moreover, when the total surface coverage in the mixed layers of polymers is high enough, nonspecific adsorption of the proteins on the surface is suppressed. The use of the presented theoretical results for the design of surface modifiers with tailored abilities for specific binding of proteins and optimal nonfouling capabilities is discussed.     

Docking studies on NSAID/COX-2 isozyme complexes using Contact Statistics analysis

Summary The selective inhibition of COX-2 isozymes should lead to a new generation of NSAIDs with significantly reduced side effects; e.g. celecoxib (Celebrex^®) and rofecoxib (Vioxx^®). To obtain inhibitors with higher selectivity it has become essential to gain additional insight into the details of the interactions between COX isozymes and NSAIDs. Although X-ray structures of COX-2 complexed with a small number of ligands are available, experimental data are missing for two well-known selective COX-2 inhibitors (rofecoxib and nimesulide) and docking results reported are controversial. We use a combination of a traditional docking procedure with a new computational tool (Contact Statistics analysis) that identifies the best orientation among a number of solutions to shed some light on this topic.     

Synthesis and characterization of Al2O3/Cr2O3-based ceramic pigments

The synthesis and the characterization of Al₂O₃-based nanocrystalline inorganic pigments are reported. The pigments were synthesized by the polymeric precursor (Pechini method) using Cr₂O₃ as chromophore. XRD results only evidenced the corundum phase. The average particle size was about 34 nm. The samples were also characterized by differential scanning calorimetry (DSC) and thermogravimetry (TG), and CIE-L*a*b* calorimetry. The pigments obtained in this work presented different colors, ranging from green to rose. This revised version was published online in August 2006 with corrections to the Cover Date.     

Effect of the modifier ion on the properties of MgFe<Subscript>2</Subscript>O<Subscript>4</Subscript> and ZnFe<Subscript>2</Subscript>O<Subscript>4</Subscript> pigments

Magnesium and zinc ferrites have been prepared by the polymeric precursor method. The organic material decomposition was studied by thermogravimetry (TG) and differential thermal analysis (DTA). The variation of crystalline phases and particle morphology with calcination temperature were investigated using X-ray diffraction (XRD) and scanning electronic microscopy (SEM), respectively. The colors of the ferrites were evaluated using colorimetry. Magnesium ferrite crystallizes above 800°C, presenting a yellow- orange color with a reflectance peak at the 600–650 nm range, while zinc ferrite crystallizes at 600°C, with a reflectance peak between 650–700 nm, corresponding to the red-brick color.     

A possible modulation of acetylcholine receptors of embryonic chick muscle cells by alpha-bungarotoxin

Acetylcholine receptors were assayed with alpha-bugarotoxin on embryonic chick skeletal muscle growing in primary cell culture. Toxin was bound specifically to muscle cells and could be competed with D-tubocurarine. Two dissociation constants were obtained by equilibrium binding: 7.2 x 10(-9)M and 2.7 x 10(-7)M at 25 degrees C. Two sets of rate constants were also obtained from dissociation kinetics. There are five times more low affinity sites on cells than high affinity sites. The average density of high-affinity receptors is about 200/micrometers2. A time course of toxin binding to receptors at 37 degrees C in growth medium revealed that under conditions permitting growth and metabolism, toxin bound to cells was lost. The possibility that the growth medium was inactivating toxin molecules was ruled out by showing that unbound toxin molecules in the medium were fully capable of binding to fresh cultures.     

Magnetic Behavior at Low Temperatures of Ti Oxide Polycrystalline Samples

Ti-oxide polycrystalline samples have been synthesized by the Pechini method and their low temperature magnetic properties have been characterized. The synthesis procedures allow the preparation of high-quality samples ensuring that the observed low temperature magnetic behavior is intrinsic to the system, not due to the polycrystalline nature of the samples. Magnetic susceptibility measurements showed that the anatase and rutile TiO₂ exhibit a paramagnetic behavior. For the CoTiO₃ samples, a totally reversible antiferromagnetic transition at 38 K is reported.     

Addition of ethyl urethane to olefins: A new approach to the synthesis of aliphatic carbamates

Several different palladium-based catalytic systems have been investigated for the addition of urethane (NH₂COOEt) to olefins. A catalytic system based on PdCl₂(CH₃CN)₂/CuCl/O₂ gave good results only in the case of the activated olefin methyl acrylate. Catalytic systems of the type Pd(acac)₂/phosphorus ligand/acid. previously used to catalyse the telomerisation of conjugated olefins with amines, gave the desired adduct. together with the product of addition of one molecule of urethane and two molecules of diolefin, in the case of isoprene and 2.3-dimethylbutadiene. The main by-products were the dimers of the diolefin, whereas the selectivity in urethane appears to be high. In no case could the addition of urethane to an unactivated non-conjugated olefin be achieved.