The Role of Carnitine Acyltransferases in the Maintenance of Cell Function

Carnitine acyltransferases catalyse equilibria between acyl-CoA esters and the respective acylcarnitines. Therefore, they act not only as pathway enzymes, but also as modulators of acyl-CoA concentrations within individual sub-cellular compartments. Because acyl-CoA esters are potent biologically active metabolites, carnitine acyltransferase activities are potentially able to affect a diverse range of physiological processes, ranging from insulin secretion, to appetite control, and insulin sensitivity of tissues. The distinctive subcellular distributions of the different types of carnitine acyltransferases also enables them to participate in the transfer of acyl moieties across intracellular membranes, and of particular acylcarnitine esters across the plasma membrane and into the plasma. Pharmacological strategies that make use of these properties to improve cell function are discussed.     

On the exotherm of polyacrylonitrile. II. Examination of deuterated polymers

A series of α-, β,β-, and α,β,β-deuterium-labelled acrylonitrile monomers were prepared and polymerized. Secondary deuterium isotope effects on the polymerization and on the pyrolysis reactions that precede carbon fiber formation were observed. When deuterium is in the α-position, the polymerization rate is greater and the molecular weight is higher. It is proposed that either the propagation rate constant or both that constant and the termination rate constant are increased on deuterium substitution. In differential scanning calorimetry, the polyacrylonitrile exotherm occurs at higher temperatures and is narrower when deuterium is substituted at the α-position. On the other hand, the thermal gravimetric analysis activation energy for weight loss of polymer at temperatures below the acrylic exotherm is lower when deuterium is in the α-position, relative to the α-hydrogen polymers. As there is no correlation between the weight loss energy of activation and the various exotherm parameters, the weight loss energy of activation and the various exotherm parameters, the weight loss and exotherm are considered to be independent events. Examination of the distribution of deuterium substituted ammonia species evolved during 100–240°C thermal treatment of the α-and β, β-deuterated polyacrylonitriles provides a clear indication that both the α- and β-positions are directly involved in hydrogen migration to nitrogen, but the mechanism of ammonia generation remains unclear. © 1995 John Wiley & Sons, Inc.     

The Constituents of the Leaves of Chamaecyparis Formosensis Matsum

Forty one terpenoidal compounds were isolated from the essential oil of Chamaecyparis formosensis Matsum. The dominant component is α-pinene. Other major components include β-pinene, 3-carene, α-terpineol, γ-muurolene, and kaurene.     

Triphenylphosphine‐Mediated Reduction of Electron‐Deficient Propargyl Ethers to the Allylic Ethers

Semihydrogenation of α,β‐unsaturated ynoates and ‐ynones bearing a γ‐alkoxy group can be performed using triphenylphosphine and water. α,β‐Unsaturated ynoates were reduced to a mixture of cis and trans α,β‐unsaturated enoates, whereas, ynones were reduced to trans α,β‐unsaturated enones as the only products.     

Structural Insights into the Role of β3 nAChR Subunit in the Activation of Nicotinic Receptors

The β3 subunit of nicotinic acetylcholine receptors (nAChRs) participates in heteropentameric assemblies with some α and other β neuronal subunits forming a plethora of various subtypes, differing in their electrophysiological and pharmacological properties. While β3 has for several years been considered an accessory subunit without direct participation in the formation of functional binding sites, recent electrophysiology data have disputed this notion and indicated the presence of a functional (+) side on the extracellular domain (ECD) of β3. In this study, we present the 2.4 Å resolution crystal structure of the monomeric β3 ECD, which revealed rather distinctive loop C features as compared to those of α nAChR subunits, leading to intramolecular stereochemical hindrance of the binding site cavity. Vigorous molecular dynamics simulations in the context of full length pentameric β3-containing nAChRs, while not excluding the possibility of a β3 (+) binding site, demonstrate that this site cannot efficiently accommodate the agonist nicotine. From the structural perspective, our results endorse the accessory rather than functional role of the β3 nAChR subunit, in accordance with earlier functional studies on β3-containing nAChRs.     

Gamma-oxidation of linear low-density polyethylene: The dose–rate effect of irradiation on chemical and physical modifications

γ-Oxidation of linear low-density polyethylene based on hexene and butene was investigated. Irradiation was performed at different dose rates in air (from 2 rad/s to 100 rad/s). Degraded samples were analyzed with IR combined with NO and SF₄ derivatizations. Our results showed that the lower the dose rate, the higher the degree of oxidation in terms of γ-product formation. Ketone species appeared to be the dominant γ-products. The G values of γ-product formation were very dependent on the dose rate of initiation. Comparison of the G value ratio of different γ-products revealed stoechiometry differences. The complex appearance and disappearance of unsaturations was tentatively explained. The modifications of elongation at break induced by γ-irradiation were monitored by molecular changes in weight. This was not conclusive because changes in elongation at break are inconsistent with changes in M_w/M_n. © 1995 John Wiley & Sons, Inc.     

New approach to the stereoselective synthesis of the [4.5] spiroketal moiety of papulacandins

An efficient approach for the stereoselective construction of the spiroketal moiety of papulacandins, based on the condensation of the protected derivative of D-arabino-1,4-lactone 2 with the α-lithiated carbanion of β-phenylsulfonyl dihydrofuran 1, is described.     

Steroidal Alkaloids from Veratrum dahuricum (Turcz.) Loes. f. with Genotoxicity on Brain Cell DNA in Mice

Two new steroidal alkaloids, 2β‐hydroxyverdine ( 1 ) and tomatillidine 3‐O‐β‐D ‐glucopyranoside ( 2 ), were isolated from the root and rhizome of Veratrum dahuricum (Turcz .) Loes . f., together with four known compounds, i.e., 16‐O‐(2‐methylbutyroyl)germine ( 3 ), veramitaline ( 4 ), jervine ( 5 ), and veratroylzygadenine ( 6 ). Their structures were established by extensive spectroscopic analysis, as well as by comparison with data in literature. Compounds 1 – 6 exhibited genotoxicity on brain cell DNA of the cerebellum and cerebral cortex in mice, evaluated by using single‐cell gel electrophoresis (comet assay).     

19F‐NMR Reveals the Role of Mobile Loops in Product and Inhibitor Binding by the São Paulo Metallo‐β‐Lactamase

Resistance to β‐lactam antibiotics mediated by metallo‐β‐lactamases (MBLs) is a growing problem. We describe the use of protein‐observe ¹⁹F‐NMR (PrOF NMR) to study the dynamics of the São Paulo MBL (SPM‐1) from β‐lactam‐resistant Pseudomonas aeruginosa . Cysteinyl variants on the α3 and L3 regions, which flank the di‐Zn^II active site, were selectively ¹⁹F‐labeled using 3‐bromo‐1,1,1‐trifluoroacetone. The PrOF NMR results reveal roles for the mobile α3 and L3 regions in the binding of both inhibitors and hydrolyzed β‐lactam products to SPM‐1. These results have implications for the mechanisms and inhibition of MBLs by β‐lactams and non‐β‐lactams and illustrate the utility of PrOF NMR for efficiently analyzing metal chelation, identifying new binding modes, and studying protein binding from a mixture of equilibrating isomers.     

Examining the levels of ganglioside and cholesterol in cell membrane on attenuation the cytotoxicity of beta-amyloid peptide

The deposition of beta-amyloid (Abeta) on cell membranes is considered as one of the primary factors in having Alzheimer's disease (AD). Recent studies have suggested that certain components of plasma membrane, ganglioside and cholesterol could accelerate the accumulation of Abeta on the plasma membranes. However, the effect of cholesterol and ganglioside (GM1) on Abeta cytotoxicity is still a controversial issue. The aim of this study is to understand the roles of GM1 and cholesterol in AD by using PC12, a neuron-like cell. The effects of the sequence, conformation, and concentration of Abeta on cytotoxicity were also investigated. Monomeric Abeta could attack the plasma membrane resulting in cytotoxicity, however, fibrillar Abeta was found to be less toxic. Our results showed that Abeta (1-40) was more toxic than Abeta (25-35) and the cytotoxicity of Abeta was proportional to its concentration. Besides, the depletion of GM1 from plasma membrane, it would block the Abeta-induced cytotoxicity. Decreasing the cholesterol level by around 30% could attenuate the cytotoxicity of Abeta. These findings validate our idea that the cholesterol could stabilize the lateral pressure derived from the formation of GM1-Abeta complex on the membrane surface. Furthermore, both GM1 and cholesterol are essential in mechanism of Abeta accumulation and could modulate the cytotoxicity of monomeric Abeta.     

A Novel Method for the Synthesis of α,β‐Unsaturated Amides Mediated by Samarium Diiodide

Promoted by Samarium diiodide (SmI₂), α,β‐unsaturated amides were formed from nitrogen anions (formed in situ by the reduction of nitro compounds) and α,β‐unsaturated esters. This reaction contrasts with the conjugate addition between amines and α,β‐unsaturated esters promoted by samarium triiodide (SmI₃) and provides an alternative attractive way to obtain α,β‐unsaturated amides using SmI₂.     

The Preparation of β-Cycloalkyl-L-Aspartate and γ-Cycloalkyl-L-Glutamate by Enzymatic Hydrolyses

The simple method to prepare the β-cycloalkyl aspartate and γ-cycloalkyl glutamate by enzymatic reactions has been developed. Compared with conventional chemical methods, the enzymatic method is more facile.     

Recent Developments in the Field of β-Lactam Antibiotics

The era of β-lactam antibiotics, which represent the most important class of drugs against infectious diseases caused by bacteria, began more than fifty years ago with the discovery of penicillin G. Further improvements by isolation and structure elucidation of new natural compounds, and systematic chemical modification of these, is a striking example of to what extent chemistry can contribute to the progress of drug therapy. The complex relationship between structure and activity requires, even today, a largely empirical approach. The minimum structural unit for antibiotic activity had to be revised several times over decades. Both the activated β-lactam ring with an acidic group and the nature and spatial arrangement of the other substituents and rings decisively affect the potency, antibacterial spectrum, pharmacokinetics, and toxicity. Totally synthetic mono- and bicyclic compounds from the series of monobactams, penems, carbapenems, 1-oxacephems, and 1-carbacephems are increasingly joining the classic groups obtained by semisynthesis from 6-amino-penicillanic acid and 7-aminophalosporanic acid.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

Diaryl-2-pyrrolidinemethanols catalyzed enantioselective epoxidation of α,β-enones: new insight into the effect of structural modification of the catalyst on reaction efficiency

Catalytic enantioselective epoxidation of α,β-unsaturated ketones promoted by diaryl-2-pyrrolidinemethanols and tert-butyl hydroperoxide (TBHP) is described. Investigation on structural modifications of the diaryl-2-pyrrolidinemethanols showed that fine tuning of the stereoelectronics of the substituents on the aryl moiety is important to achieve high efficiency. By employing a structurally optimized organocatalyst, significantly reduced loading (10 mol %) can be used to produce the epoxides in high yield and up to 90% ee at room temperature.     

The effect of annealing on the structure and relaxation processes of vinyl alcohol–ethylene copolymers

An annealing process has been applied to three samples of vinyl alcohol–ethylene (VAE) copolymers, richer in the former comonomer. The effect of such a process on the structure and on the relaxation mechanisms is studied. The structure of the three VAE copolymers has changed slightly. Nevertheless, the viscoelastic relaxation processes have been significantly affected for the thermal treatment. Two additional relaxations have appeared: one of them at temperatures above the relaxation associated to the glass transition, and the other at temperatures below the β mechanism of these copolymers. The temperature location, intensity, and apparent activation energy of the distinct relaxations found are discussed and compared with those in the original copolymers and the homopolymers, poly(vinyl alcohol) and polyethylene. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 1–12, 2001     

Gas chromatographic separation of the enantiomers of flumecinol and some related compounds

Flumecinol and related compounds can, without derivatization, be separated into their enantiomers by gas chromatography on cyclodextrin phases; permethylated β-cyclodextrin dissolved in OV-1701 can be particularly recommended. Thermodynamic data describing the different intensities of interaction of the individual enantiomers with the stationary phases were determined. The values measured imply different separation mechanisms for the compounds investigated.