Synthesis, pharmacology, and cell biology of sn-2-aminooxy analogues of lysophosphatidic acid

An efficient enantioselective synthesis of sn-2-aminooxy (AO) analogues of lysophosphatidic acid (LPA) that possess palmitoyl and oleoyl acyl chains is presented. Both sn-2-AO LPA analogues are agonists for the LPA1, LPA2, and LPA4 G-protein-coupled receptors, but antagonists for the LPA3 receptor and inhibitors of autotaxin (ATX). Moreover, both analogues stimulate migration of intestinal epithelial cells in a scratch wound assay.     

Profiling of Potential Antibacterial Compounds of Lactic Acid Bacteria against Extremely Drug Resistant (XDR) Acinetobacter baumannii

A total of 20 of isolates of lactic acid bacteria (LAB) were selected and screened for antagonistic activity against clinical strains of 30 clinical isolates of extremely drug-resistant (XDR) Acinetobacter baumannii using the well diffusion assay method. Results showed that 50% of the highly LAB strains possessed inhibitory activity against (up to 66%) of the XDR A. baumannii strains tested. The supernatant of the twenty LAB strains was subjected to gas chromatography mass spectrometry (GCMS) revealed that the common compound found in the active isolates against XDR A. baumannii was 3-Isobutyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, a known potential diketopiperazine group. The molecular docking study against potential antibacterial targets with selected ligands was performed to predict the binding mode of interactions, which is responsible for antibacterial activity. The docking analysis of the potent compounds supported the potential antibacterial activity exhibiting high inhibition constant and binding affinity in silico.     

The surface oxidation potential of melanosomes measured by free electron laser-photoelectron emission microscopy

A technique for measuring the photoionization spectrum and the photoelectron emission threshold of a microscopic structured material is presented. The theoretical underpinning of the experiment and the accuracy of the measurements are discussed. The technique is applied to titanium silicide nanostructures and melanosomes isolated from human hair, human and bovine retinal pigment epithelium cells, and the ink sac of Sepia officinalis. A common photothreshold of 4.5 +/- 0.2 eV is found for this set of melanosomes and is attributed to the photoionization of the eumelanin pigment. The relationship between the photoionization threshold and the electrochemical potential referenced to the normal hydrogen electrode is used to quantify the surface oxidation potential of the melanosome. The developed technique is used to examine the effect of iron chelation on the surface oxidation potential of Sepia melanosomes. The surface oxidation potential is insensitive to bound Fe(III) up to saturation, suggesting that the metal is bound to the interior of the granule. This result is discussed in relation to the age-dependent accumulation of iron in human melanosomes in both the eye and brain.     

Maintaining solvent accessible surface area under rotamer substitution for protein design

Although quantities derived from solvent accessible surface areas (SASA) are useful in many applications in protein design and structural biology, the computational cost of accurate SASA calculation makes SASA-based scores difficult to integrate into commonly used protein design methodologies. We demonstrate a method for maintaining accurate SASA during a Monte Carlo search of sequence and rotamer space for a fixed protein backbone. We extend the fast Le Grand and Merz algorithm (Le Grand and Merz, J Comput Chem, 14, 349), which discretizes the solvent accessible surface for each atom by placing dots on a sphere and combines Boolean masks to determine which dots are exposed. By replacing semigroup operations with group operations (from Boolean logic to counting dot coverage) we support SASA updates. Our algorithm takes time proportional to the number of atoms affected by rotamer substitution, rather than the number of atoms in the protein. For design simulations with a one hundred residue protein our approach is approximately 145 times faster than performing a Le Grand and Merz SASA calculation from scratch following each rotamer substitution. To demonstrate practical effectiveness, we optimize a SASA-based measure of protein packing in the complete redesign of a large set of proteins and protein-protein interfaces.     

Enzyme-encapsulated silica monolayers for rapid functionalization of a gold surface

We report a simple and rapid method for the deposition of amorphous silica onto a gold surface. The method is based on the ability of lysozyme to mediate the formation of silica nanoparticles. A monolayer of lysozyme is deposited via non-specific binding to gold. The lysozyme then mediates the self-assembled formation of a silica monolayer. The silica formation described herein occurs on a surface plasmon resonance (SPR) gold surface and is characterized by SPR spectroscopy. The silica layer significantly increases the surface area compared to the gold substrate and is directly compatible with a detection system. The maximum surface concentration of lysozyme was found to be a monolayer of 2.6 ng/mm(2) which allowed the deposition of a silica layer of a further 2 ng/mm(2). For additional surface functionalization, the silica was also demonstrated to be a suitable matrix for immobilization of biomolecules. The encapsulation of organophosphate hydrolase (OPH) was demonstrated as a model system. The silica forms at ambient conditions in a reaction that allows the encapsulation of enzymes directly during silica formation. OPH was successfully encapsulated within the silica particles and a detection limit for the substrate, paraoxon, using the surface-encapsulated enzyme was found to be 20 microM.     

Two-dimensional scaffolds for the parallel alignment of rod-shaped conjugated molecules

Described is a method for creating two-dimensional, ordered arrays of linear, conjugated organic molecules on polyimide scaffolds. Key to the design was the enforcement of consecutive 90 degrees twist angles along the polyimide backbone. Rod molecules that are templated by such scaffolds are held parallel and in the same plane and have optical properties that are similar to those of monomeric analogues. As supporting evidence for the structures of the polymers, a series of model compounds were synthesized and characterized by X-ray crystallography. The polymeric materials are soluble and have been characterized by 1H NMR, 13C NMR, MALDI-TOF, and UV-vis spectroscopy.     

Unusual polybrominated polypyrazolylborates and their copper(I) complexes: synthesis, characterization, and catalytic activity

Five new homoscorpionate ligands were prepared and structurally characterized as their Tl complexes, three of which, Tl[TpBr,Ph,Br] (1) (Tp = hydrotris(pyrazolyl)borate, Tl[TpBr,p-Tomicronl,Br] (2), and Tl[TpBr,p-ClPh,Br] (3), are unique in being the first examples of an "atypical" B-N bond to the most sterically hindered pyrazole nitrogen. They contain bromine atoms on the central and outer carbons of the pyrazole ring, with all aryl substituents in the 5-position of the ligand, forming a protective pocket around the B-H bond. These complexes display a rather high B-H stretch frequency (above 2 600 cm-1) in the IR region. Two other ligands, Tl[Tpp-ClPh,4Br] (4) and Tl[TpPh,Me,Br] (5), containing no outer bromine substituents, have normal B-N bonding to the least-hindered nitrogen. These new ligands have been employed to prepare the series of complexes TpxCu(NCMe) (6-10), for which X-ray studies of two of them (7 and 10) have shown that the atypical or normal geometry of the ligands is maintained when complexed to the copper center. The new complexes have also been tested as the catalysts in carbene and nitrene transfer reactions providing moderate to high yields in the expected products.     

Reaction of Ta(NMe2)5 with O2: formation of aminoxy and unusual (aminomethyl)amide oxo complexes and theoretical studies of the mechanistic pathways

Reaction of d0 Ta(NMe2)5 (1) with O2 yields two aminoxy complexes (Me2N)(n)Ta(eta2-ONMe2)(5-n) (n = 4, 2; 3, 3) as well as (Me2N)4Ta2[eta2-N(Me)CH2NMe2]2(mu-O)2 (4) and (Me2N)6Ta3[eta2-N(Me)CH2NMe2]2(eta2-ONMe2)(mu-O)3 (5) containing novel chelating (aminomethyl)amide-N(Me)CH2NMe2 ligands. The crystal structures of 2-5 have been determined by X-ray crystallography. (Me2N)4Ta(eta2-ONMe2) (2) converts to (Me2N)3Ta(eta2-ONMe2)2 (3) in its reaction with O2. In addition, the reaction of Ta(NMe2)5 with 3 gives 2 only at elevated temperatures. Density functional theory (DFT) calculations have been used to investigate the mechanistic pathways in the reactions of Ta(NMe2)5 (1) with triplet O2. Monomeric reaction pathways in the formation of 2-5 are proposed. A key step is the oxygen insertion into a Ta-N bond in 1 through an intersystem conversion from triplet to singlet energy surface to give an active peroxide complex (Me2N)4Ta(eta2-O-O-NMe2) (A4). The DFT studies indicate that the peroxide ligand plays an important role, including oxidizing an amide to an imine ligand through the abstraction of a hydride. Insertion of Me-N=CH2 into a Ta-amide bond yields the unusual -N(Me)CH2NMe2 ligands.     

The oxidation of oleate in submicron aqueous salt aerosols: evidence of a surface process

We have studied the oxidation of submicron aqueous aerosols consisting of internal mixtures of sodium oleate (oleic acid proxy), sodium dodecyl sulfate, and inorganic salts by O3, NO3/N2O5, and OH. Experiments were performed using an aerosol flow tube and a continuous flow photochemical reaction chamber coupled to a chemical ionization mass spectrometer (CIMS). The CIMS was fitted with a heated inlet for volatilization and detection of organics in the particle phase simultaneously with the gas phase. A differential mobility analyzer/condensation particle counter was used for determining aerosol size distributions. The oxidation of oleate by O3 follows Langmuir-Hinshelwood kinetics, with gammaO3 approximately 10(-5) calculated from the observed loss rate of oleate in the particle phase. The best fit Langmuir-Hinshelwood parameters are kImax=0.05+/-0.01 s-1 and KO3=4(+/-3)x10(-14) cm3molec-1. These parameters showed no dependence on the ionic composition of the aerosols or on the presence of alkyl surfactants. Several ozone oxidation products were observed to be particle-bound at ambient temperature, including nonanoic acid. We observed efficient processing of oleate by OH (0.1相似文献