DL-homoserinehydroxamic Acid,DL-homo-cystinedihydroxamic Acid,and Derivatives by Hydroxylaminolysis of γ-Hydroxy- and γ-Thio-Lactones

The reaction of α-amino-, α-carbamoylamino-, α-benzamido-, and α-benzyloxycarbonyl-amino-γ-butyrolactone with hydroxylamine led to the formation of DL-homoserinehydroxamic acid and α-N-acyl derivatives. α-N-Benzoyl-DL-homoserine-N-methyl-hydroxamic acid and O-benzylhydroxamic acid ester were prepared by reacting α-benzamido-γ-butyrolactone with N-methylhydroxylamine and with O-benzylhydroxylamine, respectively. Hydroxyl-aminolysis of DL-homocysteinethiolactone and of N-acyl-DL-homocysteinethiolactones gave homocystinedihydroxamic acid and N,N′-disubstituted derivatives. Relative reactivities of O- and S-lactones were compared.     

The Design of Potent,Selective and Drug-Like RGD αvβ1 Small-Molecule Inhibitors Derived from non-RGD α4β1 Antagonists

Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvβ1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identification of non-RGD hit small-molecule αvβ1 inhibitors. We show that αvβ1 activity is embedded in a range of published α4β1 (VLA-4) ligands; we also demonstrate how a non-RGD integrin inhibitor (of α4β1 in this case) was converted into a potent non-zwitterionic RGD integrin inhibitor (of αvβ1 in this case). We designed urea ligands with excellent selectivity over α4β1 and the other αv integrins (αvβ3, αvβ5, αvβ6, αvβ8). In silico docking models and density functional theory (DFT) calculations aided the discovery of the lead urea series.     

Natürliche Antioxidantien III Zur Kinetik der antioxidativen Wirkung von α-Tocotrienol

Natural Antioxidants III: Kinetics of Antioxidative Action of α-Tocopherols Kinetics of antioxidative action of α-tocotrienol was compared to that of other tocopherols. Specially purified methyl esters of total fatty acids of sunflower oil served as substrates, whose first ?stable”? autoxidation product is linoleic acid hydroperoxide. In all reactions studied, α-tocotrienol was somewhat more effective than α-tocopherol. The maximum inhibition was reached at a concentration of 0.02%. With increasing concentration, the well known phenomenon of reversion occurs with α-tocotrienol to a greater degree than with α-tocopherol. α-Tocotrienol, added in an amount of 0.12%, causes a more rapid decomposition of peroxides than α-tocopherol.     

Dithio and thiono. Esters. 61. Synthesis of α-Amino Dithioesters and Endothiodipeptides

The α-amino ester hydrochlorides ( 1 ) are converted into N-protected α-amino amides ( 3 ), α-amino thioamides ( 4 ) and α-amino dithiomethylesters ( 5 ). Condensation of 5 with the alkali salts of α-amino acids gives rise to the endothiodipeptide alkali salts ( 7 ).     

聚乙二醇修饰重组人IFNα_(2b)体外理化性质的初步研究

目的 分析聚乙二醇（PEG）化学修饰重组人IFNα2b（PEC-IFNα2b）的体外理化性质,并与修饰前IFNα2b进行比较。方法 将IFNα2b与PEG-IFNα2b进行胰酶消化和56℃保温实验,不同时间取样测其抗病毒活性。IFNα2b的抗体与IFNα2b和PEG-IFNα2b做双相琼脂扩散。结果 修饰后的IFNα2b的抗胰蛋白酶降解及抗热能力均明显优于未修饰的IFNα2b,抗原性亦明显下降。结论 对PEG-IFNα2b的体外理化性质进行初步分析,为研究和开发长效干扰素提供理论依据。     

Organic Fluorine Compounds. Part XLII. The Reaction of Amides of α-Bromoacids with Potassium Fluoride

The reaction of potassium fluoride with α-bromocarboxylic acid anilides, substituted in the α- or β-position, causes dehydrohalogenation and gives α, β-unsaturated anilides. Long-chain α,α′-dibromodicarboxylic acid (>C₈) anilides give in the same reaction essentially α,αprime;-di-fluorocarboxylic acid anilides.     

α-生育酚琥珀酸酯合成工艺改进的研究

本文研究了以乙二胺为催化剂,由α-生育酚和琥珀酸酐合成α-生育酚琥珀酸酯（d-TOS）N酯化反应工艺。实验结果表明用酯类溶剂有利于反应的顺利进行。本实验采用了乙酸异丁酯为溶剂,以乙二胺为催化剂的情况下使α-生育酚和琥珀酸酐反应。增大乙二胺的用量。提高琥珀酸酐与α-生育酚的配比有利于转化率的提高,但反应温度的提高,在一定范围内对转化率的提高影响不大,当大于60℃时随温度的升高转化率明显提高。实验得出α-生育酚与琥珀酸酐反应的较好工艺条件下,转化率达81．2％。     

Structural basis of Bcl-xL recognition by a BH3-mimetic α/β-peptide generated by sequence-based design

The crystal structure of a complex between the prosurvival protein Bcl-x(L) and an α/β-peptide 21-mer is described. The α/β-peptide contains six β-amino acid residues distributed periodically throughout the sequence and adopts an α-helix-like conformation that mimics the bioactive shape of the Puma BH3 domain. The α/β-peptide forms all of the noncovalent contacts that have previously been identified as necessary for recognition of the prosurvival protein by an authentic BH3 domain. Comparison of our α/β-peptide:Bcl-x(L) structure with structures of complexes between native BH3 domains and Bcl-2 family proteins reveals how subtle adjustments, including variations in helix radius and helix bowing, allow the α/β-peptide to engage Bcl-x(L) with high affinity. Geometric comparisons of the BH3-mimetic α/β-peptide with α/β-peptides in helix-bundle assemblies provide insight on the conformational plasticity of backbones that contain combinations of α- and β-amino acid residues. The BH3-mimetic α/β-peptide displays prosurvival protein-binding preferences distinct from those of Puma BH3 itself, even though these two oligomers have identical side-chain sequences. Our results suggest origins for this backbone-dependent change in selectivity.     

Phase metastability of nanosized α-Al2O3 crystallites

The reversal of the α- to θ-Al₂O₃ phase transformation and the induced microstructure evolution of boehmite-derived discrete nanosized α-crystallites are examined. Three categories of α-crystallites smaller than 100 nm were examined and found to have similar behavior: (1) pre-existing α-crystallites, (2) α-crystallites formed in situ during the calcination of θ-crystallites of sizes near the critical size, 25 nm, and (3) α-crystallites formed in situ by the thermal treatment of as-received θ-crystallites. The α-crystallite may transform back to the θ-phase above 800 °C. The backwards θ-crystallite may also re-transform to the α-phase again. Because of the density difference between α- and θ-Al₂O₃, the strain involved in the volume expansion and shrinkage during the phase transition eventually results in the formation of a twinned and/or mosaic structure for the θ- and α-crystallites. A strain release model representing the microstructure evolution of the α- to θ-phase and the θ- to α-Al₂O₃ phase transformation is proposed.     

Mehrfunktionelle N-Tenside. I. Nucleophile Substitutionen an Bischlornitrosoverbindungen. 1. Reaktionen mit Aminen,Mercaptanen und Natriumazid

Polyfunctionalized N-Tensides. I. Nucleophilic Substitutions with Bischloronitrosocompounds. 1. Reactions with Amines, Mercaptans and Sodium Azide Chloronitrosation of alkenes gives bischloronitrosocompounds 1 , which react with amines to α-aminooximes ( 2 and 4 ), with mercaptans to α-alkylthiooximes 11 , and with sodium azide to α-azidooximes 8 . Reduction with LiAlH₄ gives vicinal substituted diamines ( 6 , 7 , 10 ) from α-amino-or α-azidooximes ( 2 , 4 , 8 ) and β-alkylthioamines 13 from α-alkylthiooximes 11 . The determination of E- or Z-configuration in the α-substituted oximes is discussed.     

Production and characterization of insoluble α-1,3-linked glucan and soluble α-1,6-linked dextran from Leuconostoc pseudomesenteroides G29

Exopolysaccharides can be produced by various bacteria and have important biological roles in bacterial survival depend on molecular weight, linkage, and conformation. In this study, Leuconostoc pseudomesenteroides G29 was identified and found to produce two types of exopolysaccharides from sucrose including soluble and insoluble α-glucans. By regulation of pH above 5.5, soluble α-glucan production was increased to 38.4 g·L^-1 from 101.4 g·L^-1 sucrose with fewer accumulation of lactic acid and acetic acid. Simultaneously, the quantity of thick white precipitate, that is insoluble α-glucan, was also increased. Then, α-glucans were prepared by enzymatic reaction with crude glucansucrases from the supernatant of G29 fermentation broth and purified for structure analysis. Based on the integration analysis of FT-IR and NMR, it was observed that soluble α-glucan is a highly linear dextran with α-1,6 glycosidic bonds while the insoluble α-glucan has 93% of α-1,3 and 7% of α-1,6 glycosidic bond. The results extend our understanding of exopolysaccharides production by L. pseudomesenteroides, and this water insoluble α-1,3-glucan might have potential application as biomaterials and/or biochemicals.     

煅烧α-Al（OH）3和K2SO4混合粉末制备片晶α-Al2O3的研究

片晶α-Al2O3是一种重要的陶瓷材料,在低温下制备尺寸可控的片晶α-Al2O3具有重要的意义。通过机械球磨α-Al(OH)3和K2SO4混合粉末,然后在900℃下煅烧混合粉末,制备了片晶α-Al2O3。研究了球磨转速和混合粉末中K/Al物质的量比对所得产物晶体结构及形貌的影响。结果表明,高球磨转速能有效促进γ-Al2O3向α-Al2O3的相变过程,并导致片晶α-Al2O3的平均直径减小;K/Al物质的量比对γ-Al2O3的相变过程有很大影响。研究发现,K2SO4能够有效促进γ-Al2O3向α-Al2O3的相变;片晶α-Al2O3的生成和液相的K3Al(SO4)3有关。     

α-Tocopherol does not Accelerate Depletion of γ-Tocopherol and Tocotrienol or Excretion of their Metabolites in Rats

From an enzyme kinetic study using rat liver microsomes, α-tocopherol has been suggested to accelerate the other vitamin E catabolism by stimulating vitamin E ω-hydroxylation, the late limiting reaction of the vitamin E catabolic pathway. To test the effect of α-tocopherol on catabolism of the other vitamin E isoforms in vivo, we determined whether α-tocopherol accelerates depletion of γ-tocopherol and tocotrienol and excretion of their metabolites in rats. Male Wistar rats were fed a γ-tocopherol-rich diet for 6 weeks followed by a γ-tocopherol-free diet with or without α-tocopherol for 7 days. Intake of γ-tocopherol-free diets lowered γ-tocopherol concentrations in serum, liver, adrenal gland, small intestine, and heart, but there was no effect of dietary α-tocopherol on γ-tocopherol concentrations. The level of urinary excretion of γ-tocopherol metabolite was not affected by dietary α-tocopherol. Next, the effect of α-tocopherol on tocotrienol depletion was examined using rats fed a tocotrienol-rich diet for 6 weeks. Subsequent intake of a tocotrienol-free diet with or without α-tocopherol for 7 days depleted concentrations of α- and γ-tocotrienol in serum and tissues, which was accompanied by a decrease in the excretion of γ-tocotrienol metabolite. However, neither the tocotrienol concentration nor γ-tocotrienol metabolite excretion was affected by dietary α-tocopherol. These data showed that dietary α-tocopherol did not accelerate the depletion of γ-tocopherol and tocotrienol and their metabolite excretions, suggesting that the positive effect of α-tocopherol on vitamin E ω-hydroxylase is not sufficient to affect the other isoform concentrations in tissues.     

Creation of aggregation-defective α-synuclein variants by engineering the sequence connecting β-strand-forming domains

The aggregation of α-synuclein (αS), which is implicated in the pathology of Parkinson's disease, produces fibrils in which layers of parallel, in-register β-sheet-loop-β-sheets are formed. The effects of sequence variation in the loop-forming region (referred to as the linker region) on αS aggregation have yet to be systematically studied. In the study described here, we created and characterized αS variants containing mutations in the linker regions. Our results indicate that although the physicochemical properties of the linker region, evaluated based on an intrinsic property of a single amino acid, still play a significant role in aggregation, additional factors can also determine aggregation of αS linker mutants. Our analyses suggest that these factors include a pairwise potential for parallel in-register β-sheet formation. A linker variant displaying significantly reduced self-aggregation interfered with αS aggregation by inhibiting the conversion of αS soluble species to αS insoluble fibrils. We anticipate that linker mutations could serve as a novel method of creating αS variants that are aggregation-defective and/or inhibit αS aggregation.     

Halogenation of β-keto-sulfones using KX/H2O2 in aqueous medium: Synthesis of α-halo β-keto-sulfones and α-halomethyl sulfones

Synthesis of α-halo β-keto-sulfones and α-halomethyl sulfones is described by the reaction of β-keto-sulfones with potassium halides in the presence of hydrogen peroxide in aqueous acidic medium afforded the corresponding α-halo β-keto-sulfones at room temperature in excellent yields. Further the α-halo β-keto-sulfones on treatment of aqueous alkali underwent base-induced cleavage to yield α-halomethyl sulfones.     

α→β Sialon Transformation in Calcium-containing α-SiAlON Ceramics

Recent studies on rare earth densified α-sialon ceramics have shown that the resulting α-sialon product, present either as a single phase or in conjunction with β-sialon, is unstable when heat treated at lower (1350–1600°C) temperatures, and transforms to a mixture of β-sialon plus other crystalline or liquid metal sialon phases. The present paper describes similar studies carried out on calcium-densified α-sialon compositions, and shows that for a wide range of starting compositions, with calcium as the sole sintering additive or present with other (Nd, Sr) cations, the resulting calcium stabilised a-sialon products are fully resistant towards α⃗β transformation when heat treated in the temperature range 1450–1550°C. Whereas α⃗β transformation in rare earth stabilised α-sialons is influenced by the nature of the rare earth cation, the α-sialon composition, the composition and melting behaviour of the liquid phase and the presence or absence of β-sialon nuclei, transformation in calcium a-sialons appears to be influenced by none of these parameters. Clearly if α⃗β sialon transformation occurs in this system, the transformation temperature for calcium α-sialons must be below 1450°C, the heat-treatment temperature which has been most frequently used in current research on rare earth densified α-sialons.     

Alpha-tricalcium phosphate synthesized by two different routes: Structural and spectroscopic characterization

In the present study two alpha-tricalcium phosphate powders (αTCP-1 and αTCP-2) were synthesized by slightly different routes. For structural comparison, commercial pure α-TCP (αTCP-st) was used. The influence of the preparation method on physicochemical properties of α-TCP was investigated using scanning electron microscopy (SEM) and powder X-ray diffraction (PXRD). The chemical structure of the samples was determined using spectroscopic methods: mid-infrared spectroscopy (FT-IR), Raman spectroscopy and solid-state nuclear magnetic resonance (ssNMR). Specific surface area of the synthesized αTCP-1, αTCP-2 and standard αTCP-st powders was measured using the BET method with nitrogen adsorption. The studies have shown differences in morphology of the samples. αTCP-1 is characterized by small grains forming agglomerates below 2 µm while the αTCP-2 powder has a tendency to form compact clusters with micropores below 5 µm. Its specific surface area is about 5 times lower than αTCP-1 and close to the reference material. PXRD demonstrated that αTCP-1 is significantly less crystalline. In addition, the crystallinity of αTCP-2 was comparable to that of the standard sample. FT-IR and ssNMR experiments have indicated that αTCP-1 is not homogenous but contains beside alpha-tricalcium phosphate amorphous calcium phosphate (ACP). We suggest that ACP may be found in the interior of agglomerates and therefore it is not converted to a highly crystalline form at higher temperature. Different ways of grinding and heat treatment strongly influence characteristic properties (crystallinity, Ca/P molar ratio, phase composition, specific surface area) of the obtained αTCP.     

Phase assemblages of (Ca,Mg)-α-sialon ceramics derived from an α-sialon powder prepared by SHS

(Ca,Mg)-α-sialon powders were previously [J. Mater. Chem. 12 (2002) 1199] prepared by Self-propagating high-temperature synthesis (SHS) technology using slag as a raw material (abbreviated as Slag α-sialon powder). In this study, phase assemblages of the Slag α-sialon samples hot-pressed from 1450 to 1700 °C were investigated. Results indicated that α-sialon was the main crystalline phase in the whole sintering process, however, a small amount of β-sialon appeared in the samples sintered at 1500 °C and above. In addition, the SHS technique was also used to prepare α-sialon powders using chemical agents as raw materials (named Chem α-sialon). Samples made from the Chem α-sialon powder were hot-pressed under the same conditions for a comparison. Similar phase assemblages were obtained for the samples starting from Chem α-sialon powders, except for even more amount of βsialon phase contained. Material with a single α-sialon phase could be got in both samples when 10 wt.% additional slag and CaCO₃ were introduced into the Slag α-sialon and Chem α-sialon starting powders respectively.     

Empirical prediction method of intrinsic light scattering loss of transparent amorphous polymers

We studied simple empirical equations to estimate the values of intrinsic light scattering loss α_R of various polymers applicable for plastic optical fibers, especially for aromatic amorphous polymers. The α_R is divided into two losses, that is, α^iso and α^aniso. Here, α^iso means the isotropic scattering loss; α^aniso, the anisotropic scattering loss. The α^iso is mainly a function of refractive index, and the α^aniso is a function of refractive index, density, and the number of benzene rings in the polymer repeating unit. Therefore, when the polymer density and the structure of its repeating unit are known, the values of α_R can be estimated. We derived new empirical equations for predicting the values of each intrinsic light scattering loss, α^iso and α^aniso. The estimated values were approximately equal to the experimental ones. The values of α_R of aromatic amorphous polymers were not so large inherently, and they were a few hundred decibels per kilometer at the highest. © 1992 John Wiley & Sons, Inc.     

α-Synuclein Oligomers: A Study in Diversity

A critical step in Parkinson's disease (PD) is the formation of toxic α-synuclein oligomers (αSOs). In vitro αSOs are formed by self-assembly of α-synuclein at high concentrations, or by the addition of, for example, dopamine, lipids, ethanol, or metal ions. These αSOs are structurally distinct from the unfolded monomer and aggregated β-sheet fibrils. Nevertheless, the literature reports a wide variety of αSO shapes, sizes, and proposed toxic mechanisms. This heterogeneous character makes it difficult to form a unifying picture. Here, we present an overview of the different αSO species made in vitro, providing a tool for better comparison of different protocols and the ensuing αSOs, and emphasizing the striking versatility in the appearance and properties of these critical species. We also summarize what is known of the biological activities of different αSOs. Despite a large and increasing level of insight into αSO effects in vitro, we still lack strong insight into the structures and sizes of αSO species formed in vivo. Once this is established, it may be possible to generate more uniform protocols that could stimulate further efforts to develop viable PD biomarker assays and therapies.