bluuebunny/crossref_metadata_2025 huggingface dataset:
The VpreB1 enhancer drives developmental stage‐specific gene expression in vivo
Authors: Licence Steve , Persson Christine , Mundt Cornelia , Mårtensson Inga‐Lill
Published: March 2003

In adult mice, the VpreB genes are expressed in bone marrow progenitor (pro‐) and precursor (pre‐) B cells. As part of the pre‐B cell receptor, the proteins are crucial for the proliferation of these cells and consequently normal B lymphocyte development. Using cell lines, we identified a lineage‐ and developmental‐stage‐specific VpreB1 enhancer. Here, we analyze its specificity in vivo by generating transgenic mice in which expression of a reporter gene (human CD122) is regulated by the VpreB1 enhancer in the context of its own promoter. All transgenic lines expressed thereporter gene in the bone marrow in a copy number‐independent manner, whereas expression levels were integration site‐dependent. While the enhancer is not tissue specific, within the B cell lineage the expression pattern of human CD122 mimicked that of endogenous VpreB1. Thus, low levels were detected in pro‐B cells, high levels in pre‐BI and slightly lower levels in pre‐BII cells; no expression was detected in immature/mature B cells. Furthermore, when in vitro cultured transgenic pre‐B cells differentiated into immature B cells there was concomitant down‐regulation of human CD122 andendogenous VpreB1. Thus the VpreB1 enhancer is sufficient to ensure developmental stage‐specific expression of a reporter gene in B lymphocytes in vivo.
Dendritic cells transduced with TAT protein transduction domain‐containing tyrosinase‐related protein 2 vaccinate against murine melanoma
Authors: Shibagaki Naotaka , Udey Mark C.
Published: March 2003

Incorporation of an 11 amino acid region of the HIV TAT protein transduction domain (TAT PTD) into proteins facilitates rapid, efficient entry into cells. We previously showed that rTAT‐PTD‐OVA‐transduced dendritic cells (DC) stimulated antigen (Ag)‐specific CTL and Th cells, and vaccinated against OVA‐expressing tumors. Here we studied B16 melanoma in C57BL/6 mice, using murine tyrosinase‐related protein 2 (Trp2) as a candidate tumor Ag. We produced a 472‐amino acid N‐terminal fragment of Trp2 protein (rTrp2Δ) with or without PTD. Although PTD‐deficient rTrp2Δ was ineffective, mice given rTAT‐PTD‐Trp2Δ‐transduced DC were efficiently primed for Trp2180–188 peptide‐specific and B16‐reactive CTL. In 58% of such mice, growth of melanomas was prevented. Trp2180–188 peptide‐pulsed DC protected 35% of recipients, and irradiated GM‐CSF‐producing B16 cells protected 75%. rTAT‐PTD‐Trp2Δ‐transduced DC induced a more vigorous memory response to B16 rechallenge than the other regimens, and protected 30% of recipients from progressive tumor development in treatment studies. In this setting, Trp2 peptide‐treated DC protected 20% and irradiated GM‐CSF‐producing cells protected 0%. Both tumor prevention and tumor treatment were CD8+ T cell dependent. Vaccination with rTAT‐PTD‐Trp2Δ‐transduced DC induced a robust CTL response and durable anti‐melanoma immunity. This approach should be clinically applicable, and offers theoretical and practical advantages to those that are in current use.
IL‐7 inhibits dexamethasone‐induced apoptosis via Akt/PKB in mature, peripheral T cells
Authors: Sade Hadassah , Sarin Apurva
Published: March 2003

We have investigated the mechanism of IL‐7‐mediated inhibition of dexamethasone‐induced apoptosis in T cells. Broad‐spectrum caspase inhibitors block dexamethasone‐triggered nuclear fragmentation, but not the loss of mitochondrial transmembrane potential or membrane integrity in CD3+ mature T cells isolated from adult mouse spleens. IL‐7 blocked dexamethasone‐induced apoptosis and the processing of caspase‐3 and caspase‐7. IL‐7 also blocked dexamethasone‐triggered dephosphorylation of the serine‐threonine kinase Akt/PKB and its target, the Ser136 residue in Bad. The loss of anti‐apoptotic proteins Bcl‐xL and inhibitor of apoptosis protein‐2 (IAP‐2) was also blocked by IL‐7. The protective effect was attenuated by pharmacological inhibitors of phosphatidylinositol‐3 kinase (PI3K) with one exception: inhibition of PI3K did not abrogate Bcl‐xL expression in the presence of IL‐7. The anti‐apoptotic role of Akt suggested by these experiments was tested by overexpression of constitutively active Akt, which blocked dexamethasone‐induced apoptosis and elevated IAP‐2 but not Bcl‐xL levels in a mature T cell line. Thus, IL‐7 regulates IAP‐2 expression and inhibits dexamethasone‐induced apoptosis by activating Akt via PI3K‐dependent signaling, but regulates Bcl‐xL expression via a PI3K‐independent pathway in mature T cells.
FcγRIIB deficiency with Fas mutation is sufficient for the development of systemic autoimmune disease
Authors: Yajima Kaori , Nakamura Akira , Sugahara Akiko , Takai Toshiyuki
Published: March 2003

MRL.Faslpr/lpr mice, a model for systemic lupus erythematosus (SLE) and arthritis in humans, have a Fas mutation that results in spontaneous development of systemic autoimmune diseases and a short life span. Half of them die by 5–6 months of age due to massive progression of systemic autoimmune diseases, such as lupus nephritis. However, C57BL/6 (B6).Faslpr/lpr strain does not develop such disorders within the normal life span, indicating that suppressor gene(s) in B6 mice may control the onset and exacerbation of disease. Here, we show that the gene for a unique inhibitory Fc receptor for IgG (FcγRIIB) is a critical SLE suppressor. FcγRIIB‐deficient B6.Faslpr/lpr (B6.IIB–/–Faslpr/lpr) mice developed systemic autoimmune diseases, including anti‐DNA and anti‐type II collagen autoantibodies and cryoglobulin production, immune complex glomerulonephritis and arthritis. They were short‐lived, due to enhanced autoantibody production by B cells culminating in fatal lupus nephritis. Thus, FcγRIIB deletion with Fas mutation is sufficient for the development of systemic autoimmunity in B6 mice. The inhibitory signaling cascade via FcγRIIB may be critical for suppressing SLE in humans.
Toll‐like receptor expression in murine DC subsets: lack of TLR7 expression by CD8α+ DC correlates with unresponsiveness to imidazoquinolines
Authors: Edwards Alexander D. , Diebold Sandra S. , Slack Emma M. C. , Tomizawa Hideyuki , Hemmi Hiroaki , Kaisho Tsuneyasu , Akira Shizuo , Sousa Caetano Reis e
Published: March 2003

Toll‐like receptors (TLR) recognize microbial and viral patterns and activate dendritic cells (DC). TLR distribution among human DC subsets is heterogeneous: plasmacytoid DC (PDC) express TLR1, 7 and 9, while other DC types do not express TLR9 but express other TLR. Here, we report that mRNA for most TLR is expressed at similar levels by murine splenic DC sub‐types, including PDC, but that TLR3 is preferentially expressed by CD8α+ DC while TLR5 and TLR7 are selectively absent from the same subset. Consistent with the latter, TLR7 ligand activates CD8α– DC and PDC, but not CD8α+ DC as measured by survival ex vivo, up‐regulation of surface markers and production of IL‐12p40. These data suggest that the dichotomy in TLR expression between plasmacytoid and non‐plasmacytoid DC is not conserved between species. However, lack of TLR7 expression could restrict the involvement of CD8α+ DC in recognition of certain mouse pathogens.
What High‐Resolution Solid‐State NMR Spectroscopy Can Offer to Organic Chemists
Authors: Potrzebowski Marek J.
Published: March 2003

New applications of one‐ and two‐dimensional solid‐state NMR spectroscopy in structural studies of organic solids are presented. The review is organized into sections, the first part presenting recent progress in investigation of polymorphism and pseudo‐polymorphism phenomena. New advances in solid‐state NMR in studies of strong and weak hydrogen bonding are described in the second section, while the final part presents NMR spectroscopy as a tool with which to distinguish between enantiomers and racemates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Selective Tetrafunctionalisation of α‐Cyclodextrin using the Supertrityl Protecting Group − Synthesis of the First C2‐Symmetric Tetraphosphane Based on a Cavitand (α‐TEPHOS)
Authors: Poorters Laurent , Armspach Dominique , Matt Dominique
Published: March 2003

Regioselective tetraalkylation of α‐cyclodextrin using supertrityl chloride enables the preparation of new C2‐symmetric cavitands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Arylation of Allylic Alcohols in Ionic Liquids Catalysed by a Pd‐Benzothiazole Carbene Complex
Authors: Caló Vincenzo , Nacci Angelo , Monopoli Antonio , Spinelli Michele
Published: March 2003

The reaction of aryl bromides with allylic alcohols catalysed by a Pd‐benzothiazole carbene complex, in tetrabutylammonium bromide as solvent, leads principally to β‐arylated carbonyl compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A Convenient Generation of Acetic Acid Dianion
Authors: Parra Margarita , Sotoca Enrique , Gil Salvador
Published: March 2003

The lithium enediolate of acetic acid can be generated efficiently, as a 0.5 M solution in THF, using lithium amides prepared from n‐butyllithium in THF and either diethylamine or 1,3,3‐trimethyl‐6‐azabicyclo‐(3.2.1)‐octane (AZA). Its reaction with carbonyl compounds leads to the corresponding β‐hydroxy acids in good to moderate yields. Better yields are usually obtained when these amines are added in sub‐stoichiometric amounts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
First Synthesis, Isolation and Characterization of Enantiomerically Pure and Inherently Chiral Resorc[4]arenes by Lewis Acid Cyclization of a Resorcinol Monoalkyl Ether
Authors: Klaes Michael , Agena Ceno , Köhler Markus , Inoue Maki , Wada Takehiko , Inoue Yoshihisa , Mattay Jochen
Published: March 2003

Cyclization of resorcinol monoalkyl ethers with aliphatic aldehydes leads to the corresponding racemic mixtures of C4‐symmetric rccc‐resorc[4]arenes. Separation of these isomers was achieved by mono‐O‐functionalization of the rccc‐2,8,14,20‐tetramethylresorc[4]arene (2) with (S)‐(+)‐10‐camphorsulfonyl chloride leading to a diastereomeric mixture of (+)‐5a and (−)‐5b. After removal of the chiral auxiliary the inherently chiral pure enantiomers (+)‐2 and (−)‐2 were obtained. Further enantiomerically pure rccc‐resorc[4]arenes were obtained by cyclization of (+)‐3‐[(2S)‐2‐methylbutoxy]phenol (6) followed by chromatographic separation. The resulting diastereomeric resorc[4]arenes (+)‐7a and (−)‐7b were examined by CD spectroscopy, showing a perfect mirror image in all solvents examined. This indicates that the resorcarene cavities of (+)‐7a and (−)‐7b are essentially enantiomers of each other. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Sequential Stereoselective Catalysis: Two Single‐Flask Reactions of a Substrate in the Presence of a Bifunctional Chiral Ligand and Different Transition Metals
Authors: Annunziata Rita , Benaglia Maurizio , Cinquini Mauro , Cozzi Franco , Puglisi Alessandra
Published: March 2003

A new bifunctional ligand capable of promoting different stereoselective catalytic transformations in combination with different transition metals has been prepared by connecting with a spacer a bis(oxazoline) to dihydroquinidine; this ligand was employed in a one‐flask procedure in which methyl (E)‐3‐(4‐vinylphenyl)propenoate underwent first cyclopropanation at the electron‐rich double bond and then dihydroxylation at the electron‐poor alkene to afford a product containing four stereocenters with complete regiocontrol and high stereoselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Covalent Linkage of Melamine and Cyanurate Improves the Thermodynamic Stability of Hydrogen‐Bonded Double Rosettes in Polar Solvents
Authors: Félix Olivier , Crego‐Calama Mercedes , Luyten Ingrid , Timmerman Peter , Reinhoudt David N.
Published: March 2003

This paper describes studies on the synthesis, self‐assembly behavior, and thermodynamic stabilities of eight different calix[4]arene di(melamine‐cyanurate) or di(melamine‐barbiturate) conjugates. The successful synthetic strategy comprises the preparation of amino‐n‐alkyl‐functionalized calix[4]arene dimelamines coupled with a carboxyl‐functionalized cyanurate or barbiturate by an amide bond‐forming reaction. 1H NMR experiments show that three of the eight conjugates form well‐defined double rosette assemblies. DMSO titration experiments illustrate that the covalent linkage between the cyanurate and dimelamine moieties produces a significant increase in the thermodynamic stabilities of these conjugates. The relative stability of the assemblies seems to be primarily governed by the structure of the component connecting the melamine and cyanurate units. The highest stability (χDMSO = 70%) was observed for the di(melamine‐cyanurate) assembly in which the components are connected through an n‐heptylamidomethyl linker. Increasing the linker size from n‐heptylamidomethyl to n‐decylamidomethyl slightly reduced the thermodynamic stability (ΔχDMSO ≈︁ 10%) of the corresponding double rosette assembly. The thermodynamic stability of the double rosette structure decreases drastically, however, on introduction of substituents at the position α to the methylcarbonyl group. With benzyl substituents (based on D‐phenylalanine), neither the n‐heptyl‐ nor the n‐decylamidomethyl‐linked compounds any longer form the double rosette structure in solution. For the conjugates with a methyl substituent at this position (based on L‐alanine), only the heptyl‐linked compound still forms the double rosette structure, the χDMSO value being reduced in this case by 15%. Neither of the di(melamine‐barbiturate) conjugates form double rosette structures at all. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Formation of Triazinium‐Imidothioate Zwitterions and Their Role as Key Intermediates for Novel SN(ANRORC) Reaction Pathways (Eur. J. Org. Chem. 8/2003)
Authors: Wermann Kurt , Walther Martin , Günther Wolfgang , Görls Helmar , Anders Ernst
Published: March 2003

The cover picture shows a calculated [DFT‐(B3LYP/6‐311++G(d,p) level] “standardized” structure of the title compounds, the highly reactive triazinium‐imidothioates (center). These are readily accessible by the reaction of an amine with a bis(thiadiazolo)‐triazinium salt which is followed by deprotonation (top) and a spontaneous ring opening step. These zwitterions stabilize themselves by intramolecular cyclization reactions under the formation of either highly substituted guanidines (left) or triazolo‐thiadiazolo‐triazinium (center) or bis(triazolo)‐triazinium cations (right). Important reaction steps are initiated by negative hyperconjugation which controls the reaction modes of key intermediates. Experimental and theoretical details are discussed in the article by E. Anders et al. on p. 1389 ff.
RGD‐Porphyrin Conjugates: Synthesis and Potential Application in Photodynamic Therapy
Authors: Chaleix Vincent , Sol Vincent , Huang Yi‐Ming , Guilloton Michel , Granet Robert , Blais Jean Claude , Krausz Pierre
Published: March 2003

We report a convenient solid‐phase synthesis and characterisation of a new class of glycosylated porphyrins bearing the RGD tripeptide, designed for photodynamic cancer therapy. The photocytotoxicities of these compounds against the K562 leukemia cell line are also presented and compared to the effect of Photofrin II®. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Quantitative Gas‐Solid Diazotization of 3‐Aminopyrazolo[3,4‐b]pyridine Derivatives and Azo Dye Syntheses by Means of Solid‐Solid Reactions
Authors: Kaupp Gerd , Metwally Mohamed Abbas , Amer Fathy A. , Abdel‐latif Ehab
Published: March 2003

Gas‐solid and solid‐solid techniques allow for waste‐free quantitative syntheses and coupling reactions of the heterocyclic diazonium salts 2. The solid‐state diazotization of 1a with gaseous NO2 has been mechanistically investigated by atomic force microscopy (AFM). Azo couplings are achieved in quantitative yields by cautious co‐grinding of the solid diazonium salt 2a with five (thio)barbituric acids, six acetoacetanilides (these couplings are followed by internal cyclization in solid‐state cascades), β‐naphthol, and 2,6‐dimethylphenol. The solid diazonium salt 2a is quantitatively coupled with three solid anilines to give the tautomeric triazenes 16. The structures of the products were established with IR, NMR and mass spectroscopy, while the tautomeric properties of the compounds were judged by density functional calculations at the B3LYP/6−31G* and BLYP/6−31G** levels. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Palladium‐Catalyzed Synthesis of Nonsymmetrically Functionalized Bipyridines, Poly(bipyridines) and Terpyridines
Authors: Puglisi Alessandra , Benaglia Maurizio , Roncan Giulia
Published: March 2003

Palladium‐catalyzed coupling reactions were employed to prepare nonsymmetric, densely functionalized bipyridines and oligo(bipyridines), featuring sensitive functionalities like alcohol, ester and aldehyde groups. Stille coupling between halo(poly)pyridine and the proper (poly)pyridyltin derivative afforded in good yields nonsymmetric, derivatized oligo(bipyridines), amenable to further synthetic modifications. The methodology was used also to synthesize highly functionalized terpyridines. A series of Suzuki and Stille palladium‐promoted coupling reactions allowed us to obtain in good yields terpyridines bearing two different and differently functionalizable groups, valuable building blocks for the construction of complex supramolecular frameworks. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Denitrification Performance of Pseudomonas denitrificans in a Fluidized‐Bed Biofilm Reactor and in a Stirred Tank Reactor
Authors: Cattaneo C. , Nicolella C. , Rovatti M.
Published: March 2003

Denitrification of a synthetic wastewater containing nitrates and methanol as carbon source was carried out in two systems – a fluidized‐bed biofilm reactor (FBBR) and a stirred tank reactor (STR) – using Pseudomonas denitrificans over a period of five months. Nitrogen loading was varied during operation of both reactors to assess differences in the response to transient conditions. Experimental data were analyzed to obtain a comparison of denitrification kinetics in biofilm and suspended growth reactors. The comparison showed that the volumetric degradation capacity in the FBBR (5.36 kg N · m–3 · d–1) was higher than in the STR, due to higher biomass concentration (10 kg BM · m–3 vs 1.2 kg BM m–3).
Stability of Lycopene in Oil‐in‐Water Emulsions
Authors: Ax K. , Mayer‐Miebach E. , Link B. , Schuchmann H. , Schubert H.
Published: March 2003

Lycopene can be dissolved within the oil phase of oil‐in‐water emulsions to increase bioavailability in water‐dispersible systems. It is sensitive to oxidative conditions and easily undergoes isomerization at high temperatures. Degradation kinetics and isomerization of lycopene in oil‐in‐water‐emulsions were investigated as a function of thermal treatment and oxygen content. Lycopene degradation was found to follow a first‐order kinetics and rate constants were determined. Higher temperatures are directly correlated with increasing lycopene losses. Moreover, thermal treatment leads to a significant decrease of the concentrations of all‐trans and 13‐cis isomer, while the concentration of the 9‐cis isomer increased. Oxygen‐free conditions reduce lycopene losses significantly.
Studies on the amino acid and mineral content of buckwheat protein fractions
Authors: Wei Yi‐min , Hu Xin‐zhong , Zhang Guo‐quan , Ouyang Shao‐hui
Published: March 2003

Protein fractions were extracted by successive extraction and analysis method in four buckwheat varieties including Japanese spring buckwheat, Japanese summer buckwheat, Yuqiao No. 1 and Yuqiao 6‐21. The amino acid and the mineral content of each protein fraction were also analyzed in this paper. The basis for the data on the experiment was the relationship between protein fractions and amino acids, and the mineral contents of protein fractions. The distribution and proportion of amino acids and the minerals in each protein fraction in the buckwheat kernel as well as the nutritional value of buckwheat kernel were discussed. The results showed that there is a high amount of soluble protein and very low amount of prolamin in the buckwheat kernel. Leucine is the first limited amino acid in buckwheat, and buckwheat protein is only a seminutritional protein. The buckwheat kernel is rich in K, Zn in the albumin, Ca, Mg and Mn in the globulin, Na in the prolamin and glutelin.
Antifungal activity of peppermint and sweet basil essential oils and their major aroma constituents on some plant pathogenic fungi from the vapor phase
Authors: Edris Amr E. , Farrag Eman S.
Published: March 2003

The vapors of peppermint oil and two of its major constituents (menthol and menthone( and sweet basil oil and two of its major constituents (linalool and eugenol( were tested against Sclerotinia sclerotiorum (Lib.( Rhizopus stolonifer (Ehrenb. exFr.) Vuill and Mucorsp. (Fisher) in a closed system. These fungi cause deterioration and heavy decay of peach fruit during marketing, shipping and storage. The essential oils, their major individual aroma constituents and blends of the major individual constituents at different ratios inhibited the growth of the fungi in a dose‐dependent manner. Menthol was found to be the individual aroma constituent responsible for the antifungal properties of peppermint essential oil, while menthone alone did not show any effect at all doses. In the case of basil oil, linalool alone showed a moderate antifungal activity while eugenol showed no activity at all. Mixing the two components in a ratio similar to their concentrations in the original oil was found to enhance the antifungal properties of basil oil indicating a synergistic effect.
Influence of modified atmosphere packaging on the shelf life of prebaked pizza dough with and without preservative added
Authors: Rodríguez Valle , Medina Luis , Jordano Rafael
Published: March 2003

The possible effect of different modified atmospheres on the shelf life of prebaked pizza dough, with and without added calcium propionate, was investigated. Three packaging atmospheres were tested: 20% CO2 : 80% N2, 50% CO2 : 50% N2, 100% CO2, and air (control). Samples were examined daily for visible mold growth and analysed after 2, 8, 17 and 31 days throughout storage (15–20°C and 54–65% relative humidity, RH) for changes in gaseous composition, pH and microbial populations (mesophilic aerobic and anaerobic bacteria, lactic acid bacteria (LAB( and yeasts and molds). Microbiological results showed that molds had a greater sensitivity to CO2 than bacteria and yeasts. Products containing calcium propionate did not show mold growth throughout storage (31 days) when packaged in air or in CO2‐enriched atmospheres (20, 50 and 100%). However, in pizza dough without preservative (calcium propionate( mold growth was evident after 7 days, except under 100% CO2 atmosphere (13 days) regardless of the packaging atmosphere. From these results we conclude that the addition of calcium propionate had more and decisive influence on the shelf life extension of prebaked pizza dough.
In vitro evaluation of antioxidant properties of Cocos nucifera Linn. water
Authors: Mantena Sudheer Kumar , Jagadish  , Badduri Sridhar Reddy , Siripurapu Kiran Babu , Unnikrishnan Mazhuvancherry Kesavan
Published: March 2003

Tender Cocos nucifera L. (Palmacea) water (CW( variety Chandrasankara, was tested for its ability to scavenge free radicals, inhibit lipid peroxidation and protect hemoglobin from nitrite‐induced oxidation. Fresh sample of CW scavenged 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH( 2,2′‐azino‐bis(3‐ethylbenz‐thiazoline‐6‐sulfonic acid) (ABTS) and superoxide radicals but promoted the production of hydroxyl radicals and increased lipid peroxidation. The activity was most significant for fresh samples of CW and diminished significantly upon heat, acid or alkali treatment or dialysis. Maturity of coconut drastically decreased the scavenging ability of CW against DPPH, ABTS and superoxide radicals. CW protected hemoglobin from nitrite‐induced oxidation to methemoglobin when added before the autocatalytic stage of the oxidation. Acid, alkali or heat treated or dialyzed CW showed a decreased ability in protecting hemoglobin from oxidation. The scavenging ability and protection of hemoglobin from oxidation may be partly attributed to the ascorbic acid, which is an important constituent of CW. As CW is a rich source of vitamins, amino acids and enzymes, etc., more than one active principle may be involved.
Rapid differentiation of new apple cultivars by headspace solid‐phase microextraction in combination with chemometrical data processing
Authors: Schulz Ines , Ulrich Detlef , Fischer Christa
Published: March 2003

The aim of this study was to test a combination of automated headspace solid phase‐microextraction gas chromatography (GC) with chemometrical data treatment for the rapid differentiation of enzyme‐inactivated homogenates of new apple cultivars. The four cultivars Pinova, Piflora, Renora and Florina are characterized by different volatile patterns. Differences in the contents of volatiles were especially found for butyl acetate, ethyl butanoate, 2‐methyl butanol, ethyl acetate and 6‐methyl‐5‐hepten‐2‐ol. The used sample preparation method for GC coupled with pattern recognition of chromatograms is a useful tool for rapid and reliable determination of large numbers of samples.
Comparison of the quality of some Croatian and German wheat varieties according to the German standard protocol
Authors: Unbehend Ljiljana , Unbehend G. , Lindhauer M. G.
Published: March 2003

Ten Croatian and five German wheat varieties were tested. They were carried out using the German standard testing protocol. The results demonstrated that the quality of the Croatian wheat varieties could be ranged in A–C quality groups according to the German testing protocol. Croatian wheat varieties were comparable in many parameters (protein content, hardness, water absorption, dough handling properties and volume yield) with chosen German wheat varieties. Some differences were found in falling number, sedimentation value, flour yield, and ash value number.
Protein composition of some Croatian and German wheat varieties and their influence on the loaf volume
Authors: Unbehend Ljiljana , Unbehend G. , Lindhauer M. G.
Published: March 2003

Ten Croatian and five German wheat varieties were tested. Wheat protein composition was analysed according to a modified Osborne fractionation. They were extracted in four fractions: NaCl fraction, ethanol fraction, acetic acid fraction and insoluble fraction. The influence of protein and protein composition on the loaf volume was investigated. In protein composition a difference between the Croatian and German wheat varieties were found. Protein content, glutenin content and insoluble glutenin content showed influences on the loaf volume.
Studies on dimerisation of tocopherols under the influence of methyl linoleate peroxides
Authors: Gogolewski Marek , Nogala‐Kalucka Malgorzata , Galuba Grzegorz
Published: March 2003

The stability of plant oils is related to the level of polyunsaturated fatty acids and the presence of native antioxidants – especially tocopherols. During storage, lipids or the fat products undergo oxidation and tocopherol dimers and trimers are formed. These compounds possess reducing and antioxidant properties and participate in oxidation clearly inhibiting this process. In the present study, the correlation between levels of peroxides formed during autoxidation of methyl linoleate and simultaneous decomposition of tocopherols was examined. The peroxide value was investigated. Quantities of decomposed tocopherols and formation of their dimers were determined by high‐performance liquid chromatography (HPLC). Mass spectrum analysis confirmed that the analysed compounds were dimers. Dimerisation of γ‐T begins at the smaller quantity of the methyl linoleate peroxides than dimerisation of δ‐T. At the beginning of methyl linoleate autoxidation dimerization of γ‐T in relation to its loss was smaller. The quantity of γ‐T dimers with ether bonds in total dimers pointed to faster binding of phenoxy radicals than transformation into the phenyl ones. δ‐T dimers with phenyl bonds constitute about 65% of the total. The quantity of peroxides in methyl linoleate, necessary for quantitative and qualitative changes of homologous tocopherols, decreased from δ‐T to α‐T.
Antioxidant properties of commercial alcoholic and nonalcoholic beverages
Authors: Lugasi Andrea , Hóvári Judit
Published: March 2003

Recent interest in food phenolics has increased greatly, because of their antioxidant and free radical scavenging abilities. Popular beverages in the world include tea, coffee, cocoa, beer, wine and fruit/vegetable juices. All of these beverages contain phenolic compounds. In present study total polyphenol content and in vitro antioxidant properties were investigated in 16 red wines, 5 white wines, 5 lager beers, 3 dark beers, 17 fruit juices and 5 vegetable juices. High polyphenol content was measured in red wines (1 720 ± 546 mg·L–1) and in some fruit juices such as elderberry and prunes (5 680 and 1 807 mg·L–1, respectively). The concentration of polyphenols was between 159 and 5 680 mg·L–1in fruit juices and between 255 and 696 mg·L–1in vegetable ones, while low level of phenolics was observed in dark and lager beers and white wines (473, 376 and 392 mg·L–1, respectively). All samples exhibited significant antioxidant properties such as hydrogen‐donating ability, reducing power, chelating ability and total antioxidant status (TAS) value. These antioxidant properties strongly correlated with the total polyphenol content of the beverages.
In vitro study on digestion of peptides in Emmental cheese: Analytical evaluation and influence on angiotensin I converting enzyme inhibitory peptides
Authors: Parrot Sandrine , Degraeve Pascal , Curia Céline , Martial‐Gros Adèle
Published: March 2003

A simple in vitro protocol simulating gastrointestinal digestion of proteins and peptides to investigate the effect of digestive enzymes on the biological activity of peptides present in dairy products was developed. This protocol consisted in a 30 min incubation with pepsin followed by a 4 h incubation with trypsin or pancreatin. It was applied to an Emmental cheese water‐soluble extract (WSE) and to a casein solution (as a control). Sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) allowed to monitor the digestion of proteins. Reversed‐phase high‐performance liquid chromatography (RP‐HPLC) allowed to monitor the conversion of proteins and peptides into peptides and amino acids: it is proposed to use the mean retention time corresponding to the overall retention time distribution of molecules to assess the effect of digestive enzymes. The biological activity focused in this study was the angiotensin I converting enzyme (ACE) inhibitory activity. Digestion of Emmental WSE induced an increase of the ACE inhibition as compared to undigested WSE while a 10 kDa ultrafiltered WSE lost a part of its ACE inhibitory activity after digestion process. These results strongly suggest that digestive enzymes diminished the ACE inhibition by the peptides present in Emmental cheese WSE, while the digestion of peptides of high molecular weight would generate new ACE inhibitory peptides.
New dsDNA‐Binding Hybrid Molecules Combining an Unnatural Peptide and an Intercalating Moiety
Authors: Chaltin Patrick , Borgions Filip , Rozenski Jef , Van Aerschot Arthur , Herdewijn Piet
Published: March 2003

In our search for new dsDNA‐binding ligands, combinatorial chemistry was first applied to select unnatural oligopeptides with moderate affinity for dsDNA. To enhance the binding affinity of a heptapeptide lead structure, Ac‐Arg‐Ual‐Sar‐Chi‐Chi‐Tal‐Arg‐NH2 (Kd=4.9⋅10−4 M), the compound was conjugated to different heteropolyaromatic moieties by means of a variety of linker arms. Glycine, β‐alanine, glycyl‐glycine, glycyl‐β‐alanine, γ‐aminobutyric acid, and 6‐aminocaproic acid were used as spacers, representing different lengths and/or flexibilities. The intercalators coupled to the oligopeptide were acridine, fluorenone, anthracene, anthraquinone, and 3,8‐diamino‐5‐methyl‐6‐phenylphenantridinium (methidium). The binding capacities of these new hybrid molecules to dsDNA have been investigated by gel retardation and footprinting assays. The results show that, by conjugating the unnatural oligopeptide to intercalators, the affinity for dsDNA could be enhanced more than 100‐fold. For methidium‐β‐alanyl‐glycyl‐Arg‐Ual‐Sar‐Chi‐Chi‐Tal‐Arg‐NH2 (Kd of 2.1⋅10−6 M), the interaction with dsDNA was dominated by the intercalator in such a way that the sequence specificity of the heptapeptide was changed. The interaction with dsDNA of hybrid molecules of other intercalators was mainly governed by the oligopeptide, since the sequence selectivity of the heptapeptide was conserved. In general, the linker arm glycine (shortest spacer) and glycine‐β‐alanine were preferred over β‐alanine, glycyl‐glycine and the more‐flexible spacers γ‐aminobutyric acid and 6‐aminocaproic acid. This way new hybrid molecules endowed with dsDNA affinities of ca. 10−6 M and displaying different sequence selectivities have been developed. Therefore, combinations of such unnatural peptides with intercalators can be used to broaden the knowledge about the sequence‐selective recognition of dsDNA.
Functionalized 3,3′,5,5′‐Tetraaryl‐1,1′‐Biphenyls: Novel Platforms for Molecular Receptors
Authors: Welti Roger , Abel Yvonne , Gramlich Volker , Diederich François
Published: March 2003

This paper describes the development of novel aromatic platforms for supramolecular construction. By the Suzuki cross‐coupling protocol, a variety of functionalized m‐terphenyl derivatives were prepared (Schemes 1–4). Macrolactamization of bis(ammonium salt) (S,S)‐6 with bis(acyl halide) 7 afforded the macrocyclic receptor (S,S)‐2 (Scheme 1), which was shown by 1H‐NMR titration studies to form ‘nesting' complexes of moderate stability (Ka between 130 and 290 M−1, 300 K) with octyl glucosides 13–15 (Fig. 2) in the noncompetitive solvent CDCl3. Suzuki cross‐coupling starting from 3,3′,5,5′‐tetrabromo‐1,1′‐biphenyl provided access to a novel series of extended aromatic platforms (Scheme 5) for cleft‐type (Fig. 1) and macrotricyclic receptors such as (S,S,S,S)‐1. Although mass‐spectral evidence for the formation of (S,S,S,S)‐1 by macrolactamization between the two functionalized 3,3′,5,5′‐tetraaryl‐1,1′‐biphenyl derivatives (S,S)‐33 and 36 was obtained, the 1H‐ and 13C‐NMR spectra of purified material remained rather inconclusive with respect to both purity and constitution. The versatile access to the novel, differentially functionalized 3,3′,5,5′‐tetrabromo‐1,1′‐biphenyl platforms should ensure their wide use in future supramolecular construction.
Molecular Recognition of a Peptide by the Nickel(II) Complex of 1,4,7,10‐Tetraazacyclododecane‐2,9‐dione
Authors: Gao Jian , Reibenspies Joseph H. , Sun Yizhen , Martell Arthur E.
Published: March 2003

The nickel(II) complex of the macrocycle 1,4,7,10‐tetraazacyclododecane‐2,9‐dione (dota) was found to be efficient in the recognition of the dipeptide, glycyl‐glycine (Gly‐Gly) in aqueous solution. This (dota)NiII complex serves as a targeting molecule to form a stable ternary complex with the dipeptide at pH 8.3 in aqueous solution. The recognition constant (log K=19.20) and the recognition mechanism were investigated based on the potentiometric method. The single‐crystal of a six‐coordinated (dota)2NiII complex is also reported.
Total Synthesis of the Spermidine Alkaloid 13‐Hydroxyisocyclocelabenzine
Authors: Li Yi , Linden Anthony , Hesse Manfred
Published: March 2003

A convergent total synthesis of 13‐hydroxyisocyclocelabenzine was developed. (3S)‐Methyl 3‐amino‐3‐phenylpropanoate (4) was used as the chiral building block. The 3,4‐dihydro‐4‐hydroxyisoquinolin‐1(2H)‐one derivative (5), the key fragment for the total synthesis, was prepared by a novel base‐catalyzed lactone‐lactam ring enlargement (Scheme 3). The resulting target C(13) epimers 3a/3b from macrocyclization (Scheme 4) were separated by repeated flash chromatography. The absolute configuration of the synthetic alkaloid was determined by an X‐ray crystal‐structure analysis, which enabled us to determine the absolute configuration (9S,13R) for natural 3a with positive [α]D.
Enzyme‐Mediated Preparation of Chiral 1,3‐Dioxane Odorants
Authors: Abate Agnese , Brenna Elisabetta , Fronza Giovanni , Fuganti Claudio , Ronzani Sabrina , Serra Stefano
Published: March 2003

The enantiomerically enriched diastereoisomers of the chiral 1,3‐dioxane odorants Floropal® (1) and Magnolan® (2) were prepared by an enzyme‐mediated approach. Their olfactory properties were evaluated to investigate differences in the odor perception for the stereoisomers.
Leptosphaeric Acid, a Metabolite with a Novel Carbon Skeleton from Leptosphaeria sp. IV403, an Endophytic Fungus in Artemisia annua
Authors: Liu Jun‐Yan , Liu Chang‐Hong , Zou Wen‐Xin , Tan Ren‐Xiang
Published: March 2003

Leptosphaeric acid (1), a metabolite with a novel carbon skeleton, was isolated from the AcOEt extract of the culture of Leptosphaeria sp., an endophytic fungus (strain number: IV403) of Artemisia annua. The structure of acid 1 was elucidated on the basis of spectral analyses including homo‐ and heteronuclear correlation NMR experiments (HMQC and HMBC). The absolute configuration of the metabolite was determined by its CD and NOED studies.
A New Method for the Synthesis of Antihypercholesterolemic Agent Simvastatin
Authors: Dabak Kadir , Adiyaman Mustafa
Published: March 2003

A new synthetic method for the preparation of the cholesterol‐lowering drug simvastatin from the naturally occurring lovastatin is reported. The synthesis employs first the protection of the OH group of lovastatin (1) and then the protection of the lactone CO group to prevent enolization via conversion to the orthoesters 4a and 4b. Alkylation of the 2‐methylbutyrate side chain is then successfully achieved. Removal of the protecting groups affords antihypercholesterolemic agent simvastatin (2).
Synthesis of [4.3.3]Propellanes by Carbenium‐Ion Rearrangement and Their Olfactory Characterization
Authors: Fráter Georg , Helmlinger Daniel , Kraft Philip
Published: March 2003

Treatment of (+)‐sclareolide (1) with polyphosphoric acid or Eaton's reagent furnished, besides the anticipated cyclopentenone (−)‐12 and its isomer (−)‐15, two diastereoisomeric [4.3.3]propellanes (−)‐13 and (−)‐14, which possess interesting woody‐ambery odors. The hydrogenated derivative (−)‐17 possessed an even more‐powerful odor reminiscent of natural ambergris tincture. Mechanistic insight into this rearrangement was provided by a by‐product 24 of the reaction of sclareolide (1) with Eaton's reagent. The carbenium ion rearrangement was then employed in the synthesis of four related [4.3.3]propellanes 40–43, illustrating the utility and scope of this reaction. The olfactory properties of the synthesized [4.3.3]propellanes as well as of the original target structures 10, 33, and 34, prepared from (−)‐12 and (−)‐15, are discussed. Especially the pronounced ambra odor of (−)‐17 vividly contradicts the ‘triaxial rule of amber sensation' and provides new insight into the structural requirements for ambra odorants.
A Novel Secobetulinic Acid 3,4‐Lactone from Viburnum aboricolum
Authors: Ku Yuan‐Ling , Venkateswara Rao G. , Chen Chung‐Hsiung , Wu Chi , Guh Jih‐Hwa , Lee Shoei‐Sheng
Published: March 2003

Bio‐assay‐guided fractionation of the CHCl3‐soluble extract from the leaves of Viburnum aboricolum led to the isolation of a novel secobetulinic acid 3,4‐lactone, viburolide (=(6β)‐4,6‐dihydroxy‐3,4‐secolup‐20(29)‐ene‐3,28‐dioic acid 3,4‐lactone; 1). This is the first lupane‐type compound possessing such a lactone skeleton from natural products. Its structure was elucidated by spectral analysis and comparison with 6‐dehydroxy‐20,29‐dihydroviburolide (6) prepared from benzyl betulinate (2). Compound 6 was found to inhibit androgen‐independent human prostate cancer cells (PC‐3) with an IC50 of 12.3 μM.
A New Synthesis of Optically Active 3‐Substituted (3S)‐3,4‐Dihydro‐5‐(perfluoroalkyl)‐2H‐[1,4]oxazepin‐7‐ones
Authors: Richard Sébastien , Prié Gildas , Guignard Alain , Thibonnet Jérôme , Parrain J.‐Luc , Duchêne Alain , Abarbri Mohamed
Published: March 2003

Optically active (perfluoroalkyl)‐oxazepin‐7‐ones were synthesized in two steps starting from ethyl perfluorobut‐2‐ynoate by direct addition of optically active amino alcohols via intermolecular Michael addition and lactone formation.
New Lignan, Benzofuran, and Sesquiterpene Derivatives from the Roots of Leontopodium alpinum and L. leontopodioides
Authors: Dobner Michael J. , Ellmerer Ernst P. , Schwaiger Stefan , Batsugkh Odonchimeg , Narantuya Samdan , Stütz Michaela , Stuppner Hermann
Published: March 2003

Three new compounds, including a benzofuran, 1‐{(2R*,3S*)‐3‐(β‐D‐glucopyranosyloxy)‐2,3‐dihydro‐2‐[1‐(hydroxymethyl)vinyl]‐1‐benzofuran‐5‐yl}ethanone (1), a lignan, [(2S,3R,4R)‐4‐(3,4‐dimethoxybenzyl)‐2‐(3,4‐dimethoxyphenyl)tetrahydrofuran‐3‐yl]methyl (2E)‐2‐methylbut‐2‐enoate (2), and a silphiperfolene‐type sesquiterpene, [(1S,2Z,3aS,5aS,6R,8aR)‐1,3a,4,5,5a,6,7,8‐octahydro‐1,3a,6‐trimethylcyclopenta[c]pentalen‐2‐yl]methyl acetate (3), together with the known coumarins obliquin (4) and its 5‐methoxy derivative 5 were isolated from the roots of Leontopodium alpinum. Another known coumarin derivative, 5‐hydroxyobliquin (6), was isolated from the roots of L. leontopodioides. The structures of these compounds were established by spectroscopic studies.
Synthesis of 1,2,4‐Triazolo[4,3‐a]pyrimidine Derivatives by Cyclocondensation of a 2‐Thioxopyrimidin‐4(3H)‐one with Hydrazonoyl Halides
Authors: Elwan Nehal M. , Awad Enas M. , Hassaneen Hamdi M. , Linden Anthony , Heimgartner Heinz
Published: March 2003

The reaction of 1,2‐dihydro‐6‐(phenylamino)‐2‐thioxopyrimidin‐4(3H)one (16) with N‐arylhydrazonoyl halides 15 in CHCl3 in the presence of Et3N under reflux afforded the corresponding 1,2,4‐triazolo[4,3‐a]pyrimidin‐5‐ones of type 20 in good yields (Scheme 3). The structure of one of the derivatives, 20d, has been established by X‐ray crystallography. Conceivable reaction mechanisms are discussed in Schemes 3 and 4. The products of type 20 easily undergo reactions with electrophiles such as benzenediazonium chloride, chloroacetyl chloride, and NaNO2 in AcOH to give 6‐phenylazo, 6‐chloroacetyl, and 6‐nitroso derivatives 21, 23, and 25, respectively (Scheme 5).
Enamides via Long‐Distance Migration of Double Bonds
Authors: Sergeyev Sergey A. , Hesse Manfred
Published: March 2003

A new method for preparation of enamides (N‐(alken‐1‐yl) amides) by means of the ‘long‐distance' migration of the double bond in unsaturated amides in the presence of [Fe(CO)5] is described. The method is shown to be particularly useful for the isomerization of N‐(but‐3‐enyl)amides, while, in the case of N‐(pent‐4‐enyl) and N‐(hex‐5‐enyl) amides the mixture of products was formed and the yield of the enamide was relatively low.
Synthesis and Cytotoxicity Evaluation of Metal‐Chelator‐Bearing Flavone, Carbazole, Dibenzofuran, Xanthone, and Anthraquinone
Authors: Chen Yeh‐Long , Chen Po‐Hsu , Chung Chao‐Ho , Li Kuang‐Chieh , Jeng Haw‐Yaun , Tzeng Cherng‐Chyi
Published: March 2003

2‐(Aryloxymethyl)‐5‐benzyloxy‐1‐methyl‐1H‐pyridin‐4‐ones 8a–8g, 2‐(aryloxymethyl)‐5‐hydroxy‐4H‐pyran‐4‐ones 9a–9g, and 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a–10g were prepared from the known 5‐benzyloxy‐2‐(hydroxymethyl)pyran‐4‐one (3) in a good overall yield. These compounds were evaluated in vitro against a three‐cell lines panel consisting of MCF7 (breast), NCI‐H460 (lung), and SF‐268 (CNS), and the active compounds passed on for evaluation in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results indicated that 5‐hydroxy derivatives are more favorable than their corresponding 5‐benzyloxy precursors (10a–10g vs. 8a–8g), and 1‐methyl‐1H‐pyridin‐4‐ones are more favorable than their corresponding pyran‐4(1H)‐ones (10a–10g vs. 9a–9g). Among these three types of compounds, 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a–10g were the most cytotoxic; they inhibited the growth of almost all the cancer cells tested. On the contrary, compound 8a (a mean GI50=27.8 μM), 8b (38.5), 8d (11.0), and 8e (30.5) are especially active against the growth of SK‐MEL‐5 (a melanoma cancer cell) with a GI50 of <0.01, 5.65, 0.55, and 0.03 μM, respectively (cf. Table 2).
Effect of Through‐Bond Interaction on Conformation and Structure in Rod‐Shaped Donor–Acceptor Systems. Part 2.
Authors: De Ridder Dirk J. A. , Goubitz Kees , Schenk Henk , Krijnen Bert , Verhoeven Jan W.
Published: March 2003

The crystal structures of seven N‐aryltropan‐3‐one (=8‐aryl‐8‐azabicyclo[3.2.1]octan‐3‐one) derivatives 1T1, 2T1, 2T2, 3T2, 5T2, 2T3, and 3T3 are presented (Fig. 2 and Tables 1–5) and discussed together with the derivatives 1T2 and 4T2 published previously. The piperidine ring adopts a chair conformation. In all structures, the aryl group is in the axial position, with the plane through the aryl C‐atoms nearly perpendicular to the mirror plane of the piperidine ring. The through‐bond interaction between the piperidine ring N‐atom (one‐electron donor) and the substituted exocyclic CC bond (acceptor) not only elongates the central CC bonds of the piperidine ring but also increases the pyrimidalization at C(4) of the piperidine ring. Flattening of the C(2)–C(6) part of the piperidine ring decreases the through‐bond interaction.
Simplified Sialyl Lewisx Analogues with Improved E‐Selectin Inhibition
Authors: Thoma Gebhard , Schwarzenbach Franz
Published: March 2003

The simplified sialyl Lewisx mimic 5 containing a D‐arabinose, a 3‐cyclohexyl‐2‐hydroxypropanoate, and a tetrahydropyran building block instead of L‐fucose, sialic acid, and N‐acetylglucosamine, respectively was synthesized. Compound 5 was 10‐fold more potent than sLex in a static E‐selectin binding assay and showed at 50 μM 75% inhibition in a dynamic‐flow assay in which sLex did not inhibit neutrophil rolling at up to 1000 μM. Compound 7 with a lactic acid instead of sialic acid building block showed threefold improved potency compared to sLex.
Possible predictors of response to fluvoxamine for depression
Authors: Morishita Shigeru , Arita Seizaburo
Published: March 2003

Introduction

An investigation of the characteristics of patients being treated with antidepressants would seem to be useful in determining which patients would be most likely benefit from antidepressant medication.

Aims

The purpose of this preliminary study was to examine the possible predictors of response to fluvoxamine for depression.

Method

A retrospective cohort analysis was carried out among depression patients treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000. Seventy two patients were identified who were receiving fluvoxamine to treat depression.

Results

A variety of clinical factors including age, gender, type of depression, frequency of episodes, family history and daily dose of fluvoxamine were examined as possible predictors of the response to fluvoxamine. A Weibull regression analysis showed age, frequency of episodes and daily dose to be the independent predictive factors of improvement in fluvoxamine treatment. The most influential factor was age (ecoef = 2.109), followed by daily dose (ecoef = 0.648) and frequency of episode (ecoef = 0.512). An age of 49 years or younger (χ2 = 6.767, df = 1, p = 0.0093), a first episode (χ2 = 9.079, df = 1, p = 0.0026) and a daily dose of 100–150 mg (χ2 = 5.353, df = 1, p = 0.02) were significantly better predictors of improvement.

Conclusions

Age, the frequency of episodes and the daily dose of fluvoxamine may be considered as predictors of the response to fluvoxamine treatment for depression. This result should be examined in future prospective study. Copyright © 2002 John Wiley & Sons, Ltd.