Identification of inhibitors for UDP-galactopyranose mutase

The flavoenzyme uridine 5'-diphosphate (UDP)-galactopyranose mutase (UGM) plays a key role in the cell wall biosynthesis of many pathogens, including Mycobacterium tuberculosis. Using a synthetic fluorescent ligand, we screened 16 000 compounds in a fluorescence polarization assay. Effective inhibitors of UGM were identified.     

Reactions of dicobalt octacarbonyl and related compounds with gem-dihalides

Dicobalt octacarbonyl and some of its derivatives (NaCo(CO)₄, Co₄(CO)₁₂, Hg[Co(CO)₄]₂, [Co(CO)₃PPh₃]₂, NaCo(CO)₃PPh₃) react with activated gem-dihalides, R₂CX₂, such as dichlorodiphenylmethane, 9,9-dihalofluorenes and dimethyl dibromomalonate, to give the ‘dimer’ olefin, R₂CCR₂. The course of this conversion involves formation of the coupling product, R₂XCCXR₂, followed by dehalogenation of the latter. These separate steps have been confirmed for activated monohalides (bromodiphenylmethane, 9-bromofluorene, dimethyl bromomalonate) which were readily coupled by cobalt carbonyls, and for activated vicinal dihalides (D,L and meso-dibromostilbene, 9,9′-dichlorobisfluorenyl) which cobalt carbonyls readily dehalogenated. A radical mechanism is favored for these processes, and indirect evidence in its favor is presented.     

Energetics of protein-cyclodextrin interactions

The energetics of interaction of a range of cyclodextrins with folded and unfolded proteins has been examined by sensitive microcalorimetry techniques. Weak interaction with exposed amino acid residues promotes unfolding and dissociation of proteins. The possibility that such interactions may facilitate the use of cyclodextrins as chaperone-mimics in the refolding of denatured protein has been explored with the enzyme phosphoglycerate kinase. Up to 40% regain of activity can be achieved in some cases.     

Selenium redox cycling in the protective effects of organoselenides against oxidant-induced DNA damage

The biological role of selenium is a subject of intense current interest, and the antioxidant activity of selenoenzymes is now known to be dependent upon redox cycling of selenium within their active sites. Exogenously supplied or metabolically generated organoselenium compounds, capable of propagating a selenium redox cycle, might therefore supplement natural cellular defenses against the oxidizing agents generated during metabolism. We now report evidence that selenium redox cycling can enhance the protective effects of organoselenium compounds against oxidant-induced DNA damage. Phenylaminoethyl selenides were found to protect plasmid DNA from peroxynitrite-mediated damage by scavenging this powerful cellular oxidant and forming phenylaminoethyl selenoxides as the sole selenium-containing products. The redox properties of these organoselenoxide compounds were investigated, and the first redox potentials of selenoxides in the literature are reported here. Rate constants were determined for the reactions of the selenoxides with cellular reductants such as glutathione (GSH). These kinetic data were then used in a MatLab simulation, which showed the feasibility of selenium redox cycling by GSH in the presence of the cellular oxidant, peroxynitrite. Experiments were then carried out in which peroxynitrite-mediated plasmid DNA nick formation in the presence or absence of organoselenium compounds and GSH was monitored. The results demonstrate that GSH-mediated redox cycling of selenium enhances the protective effects of phenylaminoethyl selenides against peroxynitrite-induced DNA damage.     

Quantitation of nicotine in tobacco products by capillary electrophoresis

A simple and rapid capillary electrophoresis (CE) method was developed for the quantitation of nicotine in commercial tobacco products. The method involves a 6 min run at 30 kV, using a 50 mM phosphate buffer (pH 2.5), paraquat as internal standard, and UV detection at 260 nm. Nicotine was extracted from tobacco products in <15 min. Recoveries from spiked extracts were >95%, and the extraction efficiencies of water, 1 M HCI, 1 M acetic acid, 5 mM phosphate buffer (pH 2.5), and 1% triethanol amine were similar. Nicotine concentrations in 67 samples of cigarettes, cigars, and bidis varied between 0.37 and 2.96% (w/w). An established gas chromatography/mass spectrometry method using toluene extraction consistently yielded lower nicotine values than the CE method. Experimental evidence suggests that this is due to insufficient extraction of nicotine by toluene.     

Possible Evidence of Amide Bond Formation Between Sinapinic Acid and Lysine-Containing Bacterial Proteins by Matrix-Assisted Laser Desorption/Ionization (MALDI) at 355?nm

We previously reported the apparent formation of matrix adducts of 3,5-dimethoxy-4-hydroxy-cinnamic acid (sinapinic acid or SA) via covalent attachment to disulfide bond-containing proteins (HdeA, Hde, and YbgS) from bacterial cell lysates ionized by matrix-assisted laser desorption/ionization (MALDI) time-of-flight-time-of-flight tandem mass spectrometry (TOF-TOF-MS/MS) and post-source decay (PSD). We also reported the absence of adduct formation when using ??-cyano-4-hydroxycinnamic acid (CHCA) matrix. Further mass spectrometric analysis of disulfide-intact and disulfide-reduced over-expressed HdeA and HdeB proteins from lysates of gene-inserted E. coli plasmids suggests covalent attachment of SA occurs not at cysteine residues but at lysine residues. In this revised hypothesis, the attachment of SA is preceded by formation of a solid phase ammonium carboxylate salt between SA and accessible lysine residues of the protein during sample preparation under acidic conditions. Laser irradiation at 355?nm of the dried sample spot results in equilibrium retrogradation followed by nucleophilic attack by the amine group of lysine at the carbonyl group of SA and subsequent amide bond formation and loss of water. The absence of CHCA adducts suggests that the electron-withdrawing effect of the ??-cyano group of this matrix may inhibit salt formation and/or amide bond formation. This revised hypothesis is supported by dissociative loss of SA (?224?Da) and the amide-bound SA (?206?Da) from SA-adducted HdeA and HdeB ions by MS/MS (PSD). It is proposed that cleavage of the amide-bound SA from the lysine side-chain occurs via rearrangement involving a pentacyclic transition state followed by hydrogen abstraction/migration and loss of 3-(4-hydroxy-3,5-dimethoxyphenyl)prop-2-ynal (?206?Da).     

On a compromise social choice correspondence

This paper analyzes the compromise social choice correspondence derived from the τ-value of digraph games. Monotonicity of this correspondence is shown. A connection between several properties of social choice correspondences based on game theoretical solutions and game theoretical properties of the underlying solutions is given. Applications to several game theoretic solutions are provided.     

Facile growth of monolayer MoS<Subscript>2</Subscript> film areas on SiO<Subscript>2</Subscript>

Areas of single-layer MoS₂ film can be prepared in a tube furnace without the need for temperature control. The films were characterized by means of Raman spectroscopy, photoluminescence, low-energy electron diffraction and microscopy, and X-ray photoelectron spectroscopy and mapping. Transport measurements show n-doped material with a mobility of 0.26 cm² V^-1 s^-1.     

Oxygen and nitrogen isotopic composition of nitrate in commercial fertilizers,nitric acid,and reagent salts

Nitrate is a key component of synthetic fertilizers that can be beneficial to crop production in agro-ecosystems, but can also cause damage to natural ecosystems if it is exported in large amounts. Stable isotopes, both oxygen and nitrogen, have been used to trace the sources and fate of nitrate in various ecosystems. However, the oxygen isotope composition of synthetic and organic nitrates is poorly constrained. Here, we present a study on the N and O isotope composition of nitrate-based fertilizers. The δ¹⁵N values of synthetic and natural nitrates were 0?±?2?‰ similar to the air N₂ from which they are derived. The δ¹⁸O values of synthetic nitrates were 23?±?3?‰, similar to air O₂, and natural nitrate fertilizer δ¹⁸O values (55?±?5?‰) were similar to those observed in atmospheric nitrate. The Δ¹⁷O values of synthetic fertilizer nitrate were approximately zero following a mass-dependent isotope relationship, while natural nitrate fertilizers had Δ¹⁷O values of 18?±?2?‰ similar to nitrate produced photochemically in the atmosphere. These narrow ranges of values can be used to assess the amount of nitrate arising from fertilizers in mixed systems where more than one nitrate source exists (soil, rivers, and lakes) using simple isotope mixing models.