bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of voltage rise of high‐current arc at atmospheric pressure due to deion plates
Authors: Nakayama Kazuo , Yokomizu Yasunobu , Matsumura Toshiro , Kanamori Eiji , Kuwamura Kazuo
Published: August 2003

A molded‐case circuit breaker has deion plates to raise an arc voltage. To understand the phenomenon of a rise in an arc voltage due to deion plates, an arc current, arc voltage, and voltages between the deion plates were measured for high‐current air arc. The peak value of the arc voltage rose with a decrease in distance between the deion plates and electrodes. This rise resulted from the voltages between the deion plates. The voltage between the deion plates was found to consist of two voltages: (1) an arc‐column voltage and (2) the voltage occurring between the arc column and the surface of the deion plates. These voltages (1) and (2) proved to be 2.3 V/mm and 25 V, respectively. On the basis of these results, the expression of the arc voltage affected by the arrangement of the deion plates was derived to be a function of current. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 145(3): 17–24, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10213
Time series prediction with a neural network model based on bidirectional computation style: An analytical study and its estimation on acquired signal transformation
Authors: Wakuya Hiroshi , Shida Katsunori
Published: August 2003

Numerous studies on time series prediction have been undertaken by a variety of researchers. Most of them typically usedunidirectionalcomputation flow, that is, present signals are applied to the model as an input and predicted future signals are derived from the model as an output. On the contrary,bidirectionalcomputation style has been proposed recently and applied to prediction tasks. A bidirectional neural network model consists of two mutually connected subnetworks and performs direct and inverse transformations bidirectionally. To apply this model to time series prediction tasks, one subnetwork is trained a conventionalfutureprediction task and the other is trained an additional task forpastprediction. Since the coupling effects between the future and past prediction subsystems promote the model's signal processing ability, bidirectionalization of the computing architecture makes it possible to improve its performance. Furthermore, in order to investigate the acquired signal transformation, two kinds of chaotic time series—the Mackey–Glass time series and “Data Set A”—are adopted in this paper. As a result of computer simulations, it has been found experimentally that the direct and inverse transformations developed independently and their information integration give the bidirectional model an advantage over the unidirectional one. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 145(3): 50–60, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10232
Voltage and reactive power control in power systems by genetic algorithm considering system decomposition and control process
Authors: Aoki Hidenori , Mizutami Yoshibumi
Published: August 2003

This paper presents a new approach to optimal voltage and reactive power control based on a genetic algorithm (GA), and attempts to shorten the time of the GA, which calculates the control process. For this purpose, a network is decomposed into subsystems by means of region/area information, and the control counts of the controller are considered in the voltage and reactive power control. Therefore, some methods that give the control procedure are proposed in the GA algorithm. The effectiveness of the proposed method is demonstrated by practical 15‐ and 118‐bus systems. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 145(3): 1–16, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10242
B cell receptor signaling mediates immediate protection from Fas‐induced apoptosis upstream of caspase activation through an atypical protein kinase C isozyme and de novo proteinsynthesis
Authors: Hinshaw Jennifer A. , Mueller Carolyn M. , Scott David W. , Williams Mark S.
Published: August 2003

Signaling through the B cell receptor (BCR) of normal splenic B cells, as well as B cell lymphoma lines, can abrogate Fas‐mediated apoptosis. Using the B lymphoma line A20.2J, BCR signaling immediately inhibited Fas‐induced apoptosis upstream of caspase‐8 activation, as determined by Ile‐Glu‐Thr‐Asp‐(IETD)ase activity and cleavage of the caspase‐8 substrate Bid. Furthermore, following overexpression of a human Fas:FLICE construct, which directly induces caspase activation in a death‐inducing signaling complex‐independent manner, cells could not be protected through BCR stimulation.Co‐incubation with cycloheximide partially reversed protection from apoptosis and increased Fas‐stimulated initiator and effector caspase activation, suggesting new protein synthesis is necessary to induce protection upstream of caspase activation. Furthermore, co‐incubation with a broad‐spectrum protein kinase C (PKC) inhibitor, such as bisindolylmaleimide (Bis), also partially reversed protection from apoptosis, and examination of a panel of PKC inhibitors suggested a role for atypical isozymes in protection. Bis also acted to increase initiator and effector caspase activation upon anti‐IgG and anti‐Fas treatment. These data suggest that BCR‐induced protection is being mediated upstream of initiator caspase activation, and is partially dependent upon both PKC family members and new protein synthesis.
Down‐regulation of CD20 on B cells upon CD40 activation
Authors: Anolik Jennifer , Looney R. John , Bottaro Andrea , Sanz Iñaki , Young Fay
Published: August 2003

CD20 is a B cell‐specific surface antigen that is thought to play an important role in B cell activation and proliferation, possibly by functioning as a calcium channel or interacting with other cell surface molecules important in B cell signal transduction, such as CD40. In this study, it was found that stimulation through CD40 caused a dramatic decrease in the expression of surface CD20 in normal human B lymphocytes. Down‐regulation of CD20 was time and ligand concentration dependent, beginning as early as 15 min after incubation with CD40 ligand‐transfected fibroblasts. The rapid onset of this effect in the presence of stable steady‐state mRNA levels suggests that CD20 down‐regulation occurs at a nontranscriptional level. Confocal fluorescent microscopy indicates that CD20 and CD40 are internalized upon CD40 activation. Specifically, CD20 translocates into lipid rafts and is internalized into cytoplasmic vesicles, in a process that is inhibited by cytochalasin B andprotein kinase C antagonists. Paradoxically, one functional consequence of CD20 down‐regulation was enhanced calcium signaling upon CD20 cross‐linking. These observations support the notion that CD20 engages downstream signaling pathways that alter calcium homeostasis rather than functioning as a calcium channel itself, such signal transduction is enhanced upon CD20 internalization, and CD40 is a regulator of CD20‐mediated signaling.
Localization of peptide/MHC class II complexes in macrophages following antigen processing of viable Streptococcus pyogenes
Authors: von Delwig Alexei , Ramachandra Lakshmi , Harding Clifford V. , Robinson John H.
Published: August 2003

The subcellular localization of peptide/MHC complexes was investigated during processing of the surface M5 protein from Streptococcus pyogenes. Bone marrow‐derived macrophages were pulsed with viable S. pyogenes for 20 min followed by various periods of chase. T hybridoma cells detected complexes of one epitope, M517–31 with Ed on the surface of macrophages within 30 min of chase. In contrast, complexes with another epitope, M5308–319 with Ad peaked later. Intracellular localization of peptide/MHC‐II complexes was studied by subcellular fractionation and detection of complexes in fractions by T hybridoma cells. M517–31/Ed complexes were detected in light membrane fractions containing plasma membrane and early endosomes by 10–30 min. M5308–319/Ad complexes were detected in these light membranes after 3 h of chase. Thus, the time course of M5308–319/Ad presentation was delayed relative to M517–31/Ed. However, neither type of complex was detected at any time in fractions containing phagosomes. Both species of peptide/MHC complexes localized to endocytic compartments, indicating a role for endosomes in presentation of antigens from phagocytosed bacteria.
CD1d‐restricted NKT cells contribute to malarial splenomegaly and enhance parasite‐specific antibody responses
Authors: Hansen Diana S. , Siomos Mary‐Anne , de Koning‐Ward Tania , Buckingham Lynn , Crabb Brendan S. , Schofield Louis
Published: August 2003

CD1d‐restricted NKT cells are a novel T cell lineage with unusual features. They co‐express some NK cell receptors and recognize glycolipid antigens through an invariant T cell receptor (TCR) in the context of CD1d molecules. Upon activation through the TCR, NKT cells produce large amounts of IFN‐γ and IL‐4. It has been proposed that rapid cytokine output by activated NKT cells may induce bystander activation of other lymphoid lineages. The impact of CD1d‐restricted NKT cell activation in the induction of B cell‐mediated immune responses to infection is still unclear. We show here that CD1‐restricted NKT cells contribute to malarial splenomegaly associated with expansion of the splenic B cell pool and enhance parasite‐specific antibody formation in response to Plasmodium berghei infection. The increased B cell‐mediated response correlates with the ability of NKT cells to promote Th2 immune responses. Additionally, antibody responses against the glycosylphosphatidylinositol (GPI)‐anchored protein merozoite surface protein 1 (MSP‐1) were found to be significantly lower in CD1–/– mice compared to wild‐type animals. P. berghei‐infected MHC class II (MHCII)–/– mice also generated antibodies against MSP‐1, suggesting that antibody production against GPI‐anchored antigens in response to malaria infection can arisefrom both MHCII‐dependent and independent pathways.
Comparison of the transcriptional regulation of classical and non‐classical MHC class II genes
Authors: Hake Sandra B. , Tobin Helen M. , Steimle Viktor , Denzin Lisa K.
Published: August 2003

The class II transactivator (CIITA) regulates expression of the classical and non‐classical MHC class II genes, HLA‐DR, ‐DP, ‐DQ and ‐DM, but not the B cell‐specific HLA‐DO (DO). Here we show that only HLA‐DR expression is completely dependent on CIITA, since residual expression of HLA‐DM, ‐DP and the β chain of DQ was observed in CIITA‐deficient RJ2.2.5 cells. Although DO shows a unique expression pattern compared to other MHC class II genes, prolonged IFN‐γ treatment of HeLa cells induced DOB expression. Similar to all MHC class II promoters, the DOB promoter contains thehighly conserved W, X1, and Y boxes in addition to a putative OCT box. Mutational analysis of the DOB promoter demonstrated that the X1, Y and OCT boxes are necessary for maximum promoter activity.Furthermore, our results demonstrate that CREB‐1, RFXANK and Oct‐2 occupy the DOB promoter in vivo, However, CIITA and Bob‐1 were only minimally recruited. Finally, fusion of Bjab, a DOB‐negative B cell line, with .174 B cells that lack the complete MHC class II region (including the DO genes), lead to DO expression. These data indicate that the expression of DO is regulated by an unidentifiedfactor in B cells.
A physical and functional link between cholesterol and tetraspanins
Authors: Charrin Stéphanie , Manié Serge , Thiele Christoph , Billard Martine , Gerlier Denis , Boucheix Claude , Rubinstein Eric
Published: August 2003

By interacting with each others, the tetraspanins are thought to assemble a network of molecular interactions, the tetraspanin web. These tetraspanin/tetraspanin interactions involve in part the palmitoylation of the proteins. We show that tetraspanins interact with cholesterol as indicated by the precipitation of tetraspanin/tetraspanin complexes by digitonin, a cholesterol‐precipitating reagent, and the labeling of the tetraspanins CD9, CD81 and CD82 with a photoactivatable cholesterol in vivo. Cholesterol may participate to the interaction of tetraspanins with each other since digitonin‐precipitation of tetraspanins was correlated with their mutual interaction, and because these interactions were disrupted following cholesterol depletion by methyl‐β‐cyclodextrin (MβCD) treatment, or cholesterol sequestration by saponin. A mutant CD9 molecule lacking all palmitoylation sites was not precipitated by digitonin under conditions in which wild‐type CD9 was precipitated, indicating a role of palmitoylation for the interaction with cholesterol. Finally, upon ligation of tetraspanins on the surface of a lymphoid B cell line, the tyrosine phosphorylation of several proteins, including the vav nucleotide exchange factor, was inhibited when cells were pretreated with MβCD, and increased when they were treated with MβCD/cholesterol complexes. Thus, there is a physical and functional link between tetraspanins and cholesterol.
Clearance of Theiler's virus infection depends on the ability to generate a CD8+ T cell response against a single immunodominant viral peptide
Authors: Mendez‐Fernandez Yanice V. , Johnson Aaron J. , Rodriguez Moses , Pease Larry R.
Published: August 2003

Theiler's murine encephalomyelitis virus (TMEV) induces a chronic demyelinating disease in the central nervous system of susceptible mice. Resistance to persistent TMEV infection maps to he D locus of the major histocompatibility complex suggesting a prominent role of antiviral CTL in the protective immune response. Introduction of the Db gene into the FVB strain confers resistance to this otherwise susceptible mouse line. Infection of the FVB/Db mouse with TMEV provides a model where antiviral resistance is determined by a response elicited by a single class I molecule. Resistant mice of the H‐2b haplotype mount a vigorous H‐2Db‐restricted immunodominant response to the VP2 capsid protein. To investigate the extent of the contributionof the immunodominant T cell population in resistance to TMEV, FVB/Db mice were depleted of VP2‐specific CD8+ T cells by peptide treatment prior to virus infection. Peptide‐treated mice were not able to clear the virus and developed extensive demyelination. These findings demonstrate that the Db‐restricted CD8+ T cells specific for a single viral peptide can confer resistance to TMEV infection. Our ability to manipulate this cellular response provides a model for investigating the mechanisms mediating protection against virus infection by CD8+ T cells.
Autoimmune NZB/NZW F1 mice utilize B cell receptor editing for generating high‐affinity anti‐dsDNA autoantibodies from low‐affinity precursors
Authors: Yachimovich‐Cohen Nurit , Fischel Ruth , Bachar Neta , Yarkoni Yuval , Eilat Dan
Published: August 2003

We have previously constructed knock‐in (C57BL/6×BALB/c) F1 mice, each expressing an anti‐DNA heavy (H) chain (D42), combined with one of three different light (L) chains, namely Vκ1‐Jκ1, Vκ4‐Jκ4 or Vκ8‐Jκ5. All of these H/L chain combinations bind DNA with similar affinity and fine specificity. However, while mice carrying Vκ1‐Jκ1‐transgenic L chain were tolerized almost exclusively by L chain receptor editing, the mice expressing Vκ8‐Jκ5 L chains utilized clonal anergy as their principal mechanism of B cell tolerance. Vκ4‐Jκ4 targeted mice exhibited an intermediate phenotype. In the present study, these three H/L chain combinations were backcrossed onto the autoimmune NZB/NZW F1 mice. We find that the mechanism of clonal anergy is abrogated in these mice, but that receptor editing is maintained. Moreover, diseased NZB/NZW mice utilize L chain secondary rearrangements for the generation of high‐affinity, anti‐dsDNA‐producing B cells from low‐affinity precursors. The edited B cell clones are not deleted or anergized in the autoimmune animal; rather they are selected for activation, class‐switching and affinity maturation by somatic mutation. These results suggest that B cell receptor editing plays an important role not only in tolerance induction, but also in generating high‐affinity autoreactive B cells in autoimmune diseases.
Autoimmune uveitis induced by molecular mimicry of peptides from rotavirus, bovine casein and retinal S‐antigen
Authors: Wildner Gerhild , Diedrichs‐Möhring Maria
Published: August 2003

Antigenic mimicry of infectious agents and autoantigens is a proposed pathomechanism for autoimmune diseases. Here, we describe antigenic mimicry of a peptide from rotavirus, a nutritional protein from bovine milk (αs2‐casein) and a peptide thereof as well as a highly pathogenic peptide from retinal S‐antigen (PDSAg), a major autoantigen in experimental autoimmune uveitis in Lewis rats. Immunization of rats with the peptides and the casein protein induced uveitis, an intraocular inflammation leading to decreased vision and even blindness. The peptides elicited cross‐reactive T cell responses and uveitis in rats and were also recognized by lymphocytes and sera from uveitis patients. Oral tolerization with PDSAg, but not with rotavirus‐ and casein‐derived peptides or caseinprotein, prevented PDSAg‐induced uveitis in rats. Cofeeding of casein with cholera toxin induced uveitis in rats, suggesting that breaking oral tolerance to casein during gastrointestinal infections might also be able to initiate uveitis in humans.
The activation of Csk by CD4 interferes with TCR‐mediated activatory signaling
Authors: Marinari Barbara , Simeoni Luca , Schraven Burkhart , Piccolella Enza , Tuosto Loretta
Published: August 2003

CD4‐Lck recruitment to TCR/CD3, as well as Lck activation is essential for T cell activation. Indeed, the blockage of CD4‐Lck recruitment to TCR during antigen recognition exerts a drastic inhibitory effect on T cell activation by interfering with both early and late phases of T cell signaling. In the present work, we report a novel inhibitory mechanism by which CD4 can shut down proximal T cell‐activating signals. Indeed, we show that upon ligation of CD4 by antibodies the inhibitory kinase, p50csk, is strongly induced and prolonged during the time. In contrast, p50csk was not activated when TCR and CD4 were properly engaged by their ligands. We also demonstrate that anti‐CD4 treatment stimulated Csk kinase associated to the membrane adapter, PAG/Cbp, without affecting the total amount of Csk bound to PAG/Cbp. As a consequence, early tyrosine phosphorylation events as well as downstream signaling pathways leading to IL‐2 gene expression induced by TCRwere inhibited in anti‐CD4 pretreated cells. We suggest a new model to explain the activation of negative signals by CD4 molecule.
Different immunogenicity of H‐2 Kb‐restricted epitopes in natural variants of the hepatitis B surface antigen
Authors: Schirmbeck Reinhold , Böhm Waltraud , Fissolo Nicolas , Melber Karl , Reimann Jörg
Published: August 2003

The small hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV) has limited variability, but some serotypes and genotypes have been defined. Although no biological or pathogenetic differences could be traced to HBV serotypes, the clinical picture, response to treatment and long‐term prognosis of HBV infection may vary with the HBV genotype, possibly due to differences in specific T cell recognition of HBV antigens from different genotypes. We analyzed murine CD8+ T cell responses to two Kb‐restricted HBsAg epitopes primed by four different HBsAg variants using protein‐ and DNA‐based vaccination protocols. The Kb‐binding S208–215 epitope 1 is processed from exogenous but not endogenous HBsAg. Variants of epitope 1 differing at two positions within the epitope (ILSPFLPL in ayw/adr versus IVSPFIPL in adw2) efficiently primed cross‐reactive CD8+ T cell responses. In contrast, the exchange of an N‐terminal flanking residue (S to N) completely eliminated the immunogenicity of epitope 1. The Kb‐binding S190–197 epitope 2 is processed from endogenous but not exogenous HBsAg. A single‐residue exchange within the epitope (VWLSVIWM in ayw/adr versus VWLSAIWM in adw2) completely eliminated the immunogenicity of epitope 2. Single, conservative residue exchanges can thus give rise to diverging CD8+ T cell repertoires, suggesting an impressive complexity and flexibility of the CD8+ T cell repertoire to antigen variants from viruses with limited diversity.
In interleukin‐7‐transgenic mice, increasing B lymphopoiesis increases follicular but not marginal zone B cell numbers
Authors: Ceredig Rhodri , Bosco Nabil , Maye Patrice N. , Andersson Jan , Rolink Antonius
Published: August 2003

Follicular and marginal zone B cells constitute the vast majority of mature B cells in the adult spleen. The inter‐relationships between these two functionally and phenotypically distinct subpopulations of B cells remain unclear. In situations of decreased bone marrow B lymphopoiesis, the proportion of spleen marginal zone B cells increases, but the consequence of increasing B lymphopoiesis on marginal zone B cells has not been investigated. Using interleukin‐7‐transgenic mice, in which B lymphopoiesis is significantly increased, we show that the number of follicular B cells increased about fivefold but the number of marginal zone B cells decreased. Functional and phenotypic analysis, including in vivo bromodeoxyuridine labeling experiments, showed that marginal zoneB cells in transgenic mice were indistinguishable from controls. Mixed radiation bone marrow chimeras showed that marginal zone B cells developed equally well from both normal and transgenic adult bone marrow B cell progenitors. Taken together, these results suggest that interleukin‐7 does not influence the lineage choice between follicular and marginal zone B cells and that the number of cells ineach compartment is independently regulated.
Role of the αI domain in ligand binding by integrin αEβ7
Authors: Corps Elaine M. , Robertson Alexis , Dauncey M. Joy , Kilshaw Peter J.
Published: August 2003

The I domain of integrin αE was modeled on the crystal structure of that in CD11b and mutated to produce an open (high affinity) or closed (low affinity) conformation. K562 transfectants expressing mutant αE and wild‐type β7 were tested for adhesion to E‐cadherin‐Fc. Downward displacement of the C terminus of the αI domain with a disulfide bridge enhanced adhesion and Mn2+ dependency. Adhesion greatly exceeded that observed using wild type integrin under similar conditions. The closed integrin gave poor adhesion which was greatly improved by PMA‐induced clustering. Blocking β7 function with a βI domain‐specific antibody inhibited the wild‐type but not the locked open integrin. Isolated open αI domain expressed on K562 cells showed strong Mn2+‐dependent adhesion to E‐cadherin, whereas the wild‐type version was ineffective. αEβ7 was shown to bind to monomeric E‐cadherin but to only one component of dimeric E‐cadherin. Finally, we report that M290, a function‐blocking antibody, bound to a conformation‐sensitive epitope near the rim of the αI domain MIDAS and recognized wild‐type and closed αI domain but not the open conformation. The results broadly support the paradigm for affinity regulation by conformational change that has been established for β2 integrins. Nevertheless, for αE, the fully open conformation may represent an extreme situation that does not occur physiologically.
Cloning and characterization of the mouse homologue of the human dendritic cell maturation marker CD208/DC‐LAMP
Authors: Salaun Bruno , de Saint‐Vis Blandine , Clair‐Moninot Valérie , Pin Jean‐Jacques , Barthélemy‐Dubois Clarisse , Kissenpfennig Adrien , Peronne Catherine , Bates Elizabeth , Mattei Marie‐Geneviève , Lebecque Serge
Published: August 2003

DC‐LAMP, a member of the lysosomal‐associated membrane protein (LAMP) family, is specifically expressed by human dendritic cells (DC) upon activation and therefore serves as marker of human DCmaturation. DC‐LAMP is detected first in activated human DC within MHC class II molecules‐containing compartments just before the translocation of MHC class II‐peptide complexes to the cell surface, suggesting a possible involvement in this process. The present study describes the cloning and characterization of mouse DC‐LAMP, whose predicted protein sequence is over 50% identical to the human counterpart. The mouse DC‐LAMP gene spans over 25 kb and shares syntenic chromosomal localization (16B2‐B4 and 3q26) and conserved organization with the human DC‐LAMP gene. Analysis of mouse DC‐LAMP mRNA and protein revealed the expression in lung peripheral cells, but also its unexpected absence from mouse lymphoid organs and from mouse DC activated either in vitro or in vivo. In conclusion, mouse DC‐LAMP is not a marker of mature mouse DC and this observation raises new questions regarding the role of human DC‐LAMP in human DC.
Generation of a transgenic animal model of hyperthyroid Graves' disease
Authors: Kim‐Saijo Misa , Akamizu Takashi , Ikuta Koichi , Iida Yasuhiko , Ohmori Katsuyuki , Matsubara Kazumi , Matsuda Yoichi , Suzuki Misao , Matsuda Fumihiko , Nakao Kazuwa
Published: August 2003

Graves' disease (GD) is an organ‐specific autoimmune disease characterized by hyperthyroidism. Agonistic anti‐thyrotropin receptor antibodies (thyroid‐stimulating antibodies, TSAb), whichmimic the thyrotropin (TSH) action, are thought to cause GD. The precise immunological mechanism of TSAb production, however, remains elusive. Previous immunization approaches using TSH receptor led to transient hyperthyroidism, but did not seem sufficient for comprehensive understanding of the development of autoimmune responses. To create GD‐related autoimmunity in mice, we here generated TSAb‐transgenic mice in which a patient‐derived TSAb is expressed in B cells. Expression of the human TSAb in mice resulted in various manifestations of hyperthyroidism including increased free thyroxine levels with concomitantly decreased TSH levels, increased thyroid uptake of technetium pertechnetate, hyperthermia and thyroid hyperplasia. We found a correlation between the serum levels of human TSAb immunoglobulin and free thyroxine. In addition, conventional B cells expressing the TSAb were partially deleted in the periphery while B1 cells expressing the TSAb persisted and accumulated in the peritoneal cavity, a finding consistent with previous demonstrations that the maintenance of B1 cells plays an important role in the development of autoimmune diseases. Thus, our transgenic mouse mayprovide a novel and useful animal model for elucidating the pathogenesis and pathophysiology of GD.
Synthesis of Polyhydroxylated Aminocyclopentanes
Authors: Kummeter Markus , Kazmaier Uli
Published: August 2003

Polyhydroxylated aminocyclopentanes are an interesting class of glycosidase inhibitors. The reactions between chelated α‐allylglycine esters and crotonaldehyde gave the corresponding aldol products in good yields and selectivities. Those compounds could be converted into enantiopure polyhydroxylated aminocyclopentanes by ring‐closing metathesis, enzymatic separation and dihydroxylation. In the final deprotection step, three different protection groups were removed simultaneously in excellent yield, either by reduction or by basic hydrolysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Native Chemical Ligation with Aspartic and Glutamic Acids as C‐Terminal Residues: Scope and Limitations
Authors: Villain Matteo , Gaertner Hubert , Botti Paolo
Published: August 2003

A new side reaction during Native Chemical Ligation (NCL) at aspartic and glutamic acid/cysteine ligation sites is reported. To exploit NCL at these sites, test peptides having either a C‐terminal unprotected aspartyl or glutamyl thioester were ligated with a peptide containing an N‐terminal free cysteine generating, in each case, two major compounds having equal masses but different retention times by HPLC analysis. Comparison of these ligation products with reference peptides of identical sequence synthesized by total SPPS (solid phase peptide synthesis) with both natural and unnatural backbones at the cysteinyl residue is in agreement with the hypothesis of migration of the thioester moiety on the side chain carboxyl group of both C‐terminal Asp and Glu residues. Enzymatic digestion of the purified ligation products with a V8‐protease further confirmed the nature of the side reaction, with a total resistance of the non‐natural backbone peptide to the protease. To overcome this problem the use of a protecting group stable to both HF cleavage and ligation conditions, but removable after ligation, became a necessity. A series of side‐chain protected derivatives were selected, specifically 9‐fluorenylmethyl ester (OFm), (phenylsulfonyl)ethyl ester (OPse), 2,2,2‐trichloroethyl ester (OTce), and phenacyl esters (OPac). For the glutamic acid, OPse gave the best results, generating the correct peptide and avoiding the isomerization at the γ‐carboxyl group. In the case of the aspartic residue, all the protecting groups were removed under basic conditions, worsening the problem and generating, for example, 70% yield of the β‐isomer after OFm deprotection. This prompted us to propose a protecting group derived from the phenacyl ester 1‐methyl‐2‐oxo‐2‐phenylethyl ester (OMop). This protecting group showed greater stability during the ligation reaction than OPac and OTce, and was easily removed by Zn/acetic acid reduction after the ligation step. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Pyrrolo‐Tetrathiafulvalenes and Their Applications in Molecular and Supramolecular Chemistry
Authors: Jeppesen Jan O. , Becher Jan
Published: August 2003

Although tetrathiafulvalene and its derivatives have been extensively studied as π‐electron donors in the fields of molecular organic metals and electrically conducting materials for more than 30 years, the intriguing potential of tetrathiafulvalene as a building block in molecular and supramolecular chemistry has only recently been developed. Progress in synthetic tetrathiafulvalene chemistry has enabled the preparation of elaborate molecular architectures and, in recent years, tetrathiafulvalene has been incorporated into a number of molecular and supramolecular systems. In this microreview we describe the background to our interest in the development of the parent pyrrolo‐tetrathiafulvalenes, followed by a journey through their applications in macrocyclic, molecular, and supramolecular chemistry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Monocyclic and Bicyclic Imino Sugars
Authors: Kummeter Markus , Kazmaier Uli
Published: August 2003

A diastereoselective aldol reaction between the chelated alanine ester enolate 5 and the protected threose derivative 6, followed by cyclization under Mitsunobu conditions, gave the pipecolinic acid derivative 9. This compound could easily be converted into the versatile protected derivative 11, which could be transformed in excellent yields either into the corresponding piperidine imino sugar 14 or into the unnatural amino acid 17. The imino alcohol 13, an intermediate in the synthesis of imino sugar 14, was also used in a straightforward approach to indolizidinone 19, involving an intramolecular Horner−Emmons reaction for ring‐closure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis, NMR Spectroscopic Characterization and Polysiloxane‐Based Immobilization of the Three Regioisomeric Monooctenylpermethyl‐β‐cyclodextrins and Their Application in Enantioselective GC
Authors: Cousin H. , Trapp O. , Peulon‐Agasse V. , Pannecoucke X. , Banspach L. , Trapp G. , Jiang Z. , Combret J. C. , Schurig V.
Published: August 2003

2I−VI,3I−VII,6I−VII‐Eicosa‐O‐methyl‐2I‐O‐(oct‐7‐enyl)cyclomaltoheptaose, 2I−VII,3I−VI,6I−VII‐eicosa‐O‐methyl‐3I‐O‐(oct‐7‐enyl)cyclomaltoheptaose, and 2I−VII,3I−VII,6I−VI‐eicosa‐O‐methyl‐6I‐O‐(oct‐7‐enyl)cyclomaltoheptaose were synthesized by selective introduction of an oct‐7‐enyl group at one of theO‐2,O‐3, orO‐6 positions of selectively methylated cyclomaltoheptaose (β‐cyclodextrin, CD) and, depending on the synthetic route, by a subsequent permethylation step. Each of the regioisomeric mono‐oct‐7‐enylated permethylated β‐cyclodextrin derivatives was anchored by hydrosilylation to a hydridomethyldimethylsiloxane copolymer to yield unambiguouslyO‐2‐,O‐3‐, andO‐6‐bonded chiral stationary phases (CSP) of Chirasil‐Dex, which were evaluated in enantioselective gas chromatography (GC).O‐6‐Chirasil‐Dex displayed slightly inferior enantioselectivity relative to eitherO‐3‐ orO‐2‐Chirasil‐Dex. The statistical synthesis of the CSP by mono‐oct‐7‐enylation of β‐CD under varying reactions conditions (base, solvent), without the use of hydroxy group protection chemistry, furnished a mixture ofO‐6‐ andO‐2‐Chirasil‐Dex in dimethylformamide and predominantly theO‐2‐regioisomer in dimethyl sulfoxide. Chirasil‐Dex, previously formulated exclusively as theO‐6 regioisomer, should be revised as anO‐2‐ andO‐6‐Chirasil‐Dex mixture. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of N‐Phenyl‐N′‐pyrimidylurea Derivatives by Selenium‐ or Selenium Dioxide‐Catalyzed Reductive Carbonylation of Nitroaromatics
Authors: Chen Jinzhu , Ling Gang , Lu Shiwei
Published: August 2003

Forty unsymmetric N‐phenyl‐N′‐pyrimidylurea derivatives were synthesized in moderate‐to‐good yields by one‐pot reductive carbonylation of nitroaromatics using selenium or selenium dioxide as the catalyst, aminopyrimidine derivatives as co‐reagents, and carbon monoxide as the carbonyl source. The reaction parameters were investigated, as was the reusability of the catalysts. We found that selenium‐ or selenium dioxide‐catalyzed reductive carbonylation of the nitroaromatics exhibited reaction‐controlled phase‐transfer phenomena of the catalysts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis and Electrochemical Studies of New Antimalarial Endoperoxides
Authors: Najjar Fadia , Baltas Michel , Gorrichon Liliane , Moreno Yolande , Tzedakis Theodore , Vial Henri , André‐Barrès Christiane
Published: August 2003

Structural analogues of endoperoxides belonging to the family of G factors have been synthesized under Mannich‐type conditions. The structures of the different diastereoisomers have been established from NMR spectroscopic data. Their cathodic peak potentials have been determined by thin layer electrochemistry under potentiostatic conditions, and compared to artemisinin. These endoperoxides were evaluated in vitro against Plasmodium falciparum and showed moderate to good activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
An Expeditious Preparation of 15‐Membered Nitrogen‐Containing Olefinic and Benzo Macrocycles
Authors: Sebastián Rosa M. , Moreno‐Mañas Marcial , Vallribera Adelina
Published: August 2003

(E,E)‐1,6,11‐Tris(arenesulfonyl)‐3,4‐benzo‐1,6,11‐triazacyclopentadeca‐8,13‐dienes (2) and 1,6,11‐tris(arenesulfonyl)‐3,4; 8,9;13,14‐tribenzo‐1,6,11‐triazacyclopentadecanes (3) were prepared from arenesulfonamides, trans‐1,4‐dibromobutene, and 1,2‐bis(bromomethyl)benzene. They form unstable complexes with silver tetrafluoroborate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of 1‐(m‐Hydroxybenzyl)‐Substituted 1,2,3,4‐Tetrahydroisoquinoline‐3‐carboxylic Acid Derivatives as Opioid Peptide Mimetics − Unexpected Amide Bond Cleavages under Mild Conditions
Authors: Mannekens Els , Crisma Marco , Van Cauwenberghe Sylvia , Tourwé Dirk
Published: August 2003

N‐Glycyl‐(1R,3S)‐1‐(m‐hydroxybenzyl)‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic) was prepared as a Tyr‐Tic dipeptide mimetic for exploration of its potential as a delta opioid receptor selective ligand. The compound was successfully obtained by a stereoselective synthesis starting from L‐Tic. In the course of the reactions, unusual peptide bond cleavages were observed under mild conditions, and reaction mechanisms have been proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A Versatile Route to Functionalized Dilactones as Monomers for the Synthesis of Poly(α‐hydroxy) Acids
Authors: Leemhuis Mark , van Steenis Jan Hein , van Uxem Michelle J. , van Nostrum Cornelus F. , Hennink Wim E.
Published: August 2003

A synthetic pathway to functionalized six‐membered dilactones structurally analogous to lactide is described. Through the use of orthogonal protecting groups, the synthesis of functionalized dilactones was performed in a straightforward way by cyanuric chloride‐mediated cyclization of the corresponding linear α‐hydroxy acid dimers. The synthesis of three different dilactones − methylglycolide, benzyloxymethylglycolide, and 2‐benzyloxymethyl‐5‐methylglycolide − by the same procedure demonstrated the versatility of this route. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
One‐Pot Synthesis of 6‐Hydroxyisochromans: The Example of Demethyl‐oxa‐coclaurine
Authors: Guiso Marcella , Bianco Armandodoriano , Marra Carolina , Cavarischia Claudia
Published: August 2003

Using a modified oxa‐Pictet Spengler reaction that we recently described, we synthesized 6‐hydroxy‐isochromans and their 7‐hydroxy derivatives. The successful one step synthesis did not require protecting groups and provided high yields. The obtainment of 1‐(4′‐hydroxybenzyl)‐6,7‐dihydroxyisochroman (1) indicates that this protocol can be used to synthesize oxygenated analogues of benzyl‐tetrahydroisoquinoline alkaloids, such as demethyl‐coclaurine (2). This methodology could provide a general procedure for the synthesis of hydroxyisochromans. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Solvolysis of Some Arenediazonium Salts in Binary EtOH/H2O Mixtures under Acidic Conditions
Authors: Pazo‐Llorente Román , Bravo‐Díaz Carlos , González‐Romero Elisa
Published: August 2003

We have determined the product distribution, the rate constants for dediazoniation product formation, and the solvolytic rate constants for 2‐, 3‐, and 4‐methylbenzenediazonium ions (2‐, 3‐, and 4‐MBD, respectively) loss in acidic ethanol/water mixtures over the whole composition range by a combination of spectrophotometric (UV/Vis) and high performance liquid chromatography (HPLC) measurements. The observed rate constants (kobs) for substrate loss are equal to those for product formation, and they remain essentially constant (2‐MBD) with changing solvent composition but increase by a factor of ≈︁2 (4MBD) on going from water to 100% EtOH. Up to four dediazoniation products − cresols (ArOH), chlorotoluene (ArCl), methylphenetole (ArOEt), and toluene (ArH) − were detected, depending on the solvent composition; the major dediazoniation products were the ArOH and ArOEt derivatives. The product selectivity (S) of the reaction towards nucleophiles is low and essentially constant with changing solvent composition, and good linear correlations between log kobs and YCl (solvent ionizing power) were observed for the three ArN2+ ions. All data are consistent with the rate‐determining formation of an aryl cation, which reacts immediately with available nucleophiles. The data suggest that the distribution of neutral and anionic nucleophiles in the neighborhood of the ground state arenediazonium ion remains essentially unchanged upon dediazoniation, the observed product distribution reflecting the concentrations of nucleophiles in their immediate environment (i.e., in the first solvation shells of the arenediazonium ions). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Choice of Phosphane Reagent in Fukuyama−Mitsunobu Alkylation: Intramolecular Selectivity Between Primary and Secondary Alcohols in the Preparation of Asymmetric Tetraamine Building Blocks for Synthesis of Philanthotoxins
Authors: Olsen Christian A. , Jørgensen Malene R. , Witt Matthias , Mellor Ian R. , Usherwood Peter N. R. , Jaroszewski Jerzy W. , Franzyk Henrik
Published: August 2003

Philanthotoxin‐433 (PhTX‐433) is a polyamine wasp toxin that antagonizes certain ionotropic receptors noncompetitively. Four analogues of PhTX‐433, C‐methylated in the polyamine chain, were synthesized from (RS)‐1,3‐butanediol, two diamine building blocks, and an activated/protected tyrosine derivative. Use of a phosphane reagent more bulky than trimethylphosphane gave a high intramolecular selectivity between primary and secondary hydroxy groups in the Fukuyama−Mitsunobu reaction. Thus, trimethylphosphane proved to be the only phosphane reagent that enabled alkylation of 2‐nitrobenzenesulfonamides with a wide range of secondary alcohols, whereas tributylphosphane was selective for primary alcohol groups. This selectivity was utilized to obtain orthogonally protected, asymmetric, branched tetraamines, employed for solution‐phase synthesis of philanthotoxin analogues. The branched philanthotoxin analogues thus obtained were tested in an electrophysiological assay using rat brain ionotropic glutamate receptors expressed in Xenopus laevis oocytes. Their potencies proved to be similar to the corresponding nonbranched analogues. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Manipulating L‐Aspartic and L‐Glutamic Acids − Diastereoselective Synthesis of Enantiopure β‐Amino‐γ‐hydroxy Acids and γ‐Amino‐δ‐hydroxy Acids
Authors: Andrés José M. , Muñoz Eva M. , Pedrosa Rafael , Pérez‐Encabo Alfonso
Published: August 2003

Enantiopure (3S,4R)‐ and (3S,4S)‐3‐amino‐4‐hydroxyhexanoic acids and (4S,5R)‐ and (4S,5S)‐4‐amino‐5‐hydroxyheptanoic acid derivatives have been prepared by stereodivergent synthesis from L‐aspartic and L‐glutamic acids, respectively. The stereochemistry at the carbon atom attached to the amino group was determined from the starting material, but the configuration at C‐4 or C‐5 is controlled by diastereoselective alkylation with diethylzinc or ethylmagnesium bromide. The protection of the carboxylic group as OBO orthoester improved the yields in the final products. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of the Tetracyclic Bis(acetal) Lactone Portion of Saudin
Authors: Labadie Guillermo R. , Luna Liliana E. , Gonzalez‐Sierra Manuel , Cravero Raquel M.
Published: August 2003

Two synthetic approaches towards the synthesis of the tetracyclic lactone 4, containing the caged bis(acetalic) backbone of Saudin, were explored. Both sequences included the utilization of the known epoxy‐acetal 3, prepared stereoselectively by means of an intramolecular radical cyclization, as the common key intermediate, allowing total control over the relative stereochemistry of four consecutive chiral centers. Oxidative degradation with ruthenium dioxide and unsymmetrical ozonolysis reactions provided the new two key synthons in each synthetic route. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Dimethoxydimethylsilane from Silicon Atoms and Dimethyl Ether: A Combined Matrix‐Spectroscopic and Density Functional Theory Study
Authors: Maier Günther , Glatthaar Jörg
Published: August 2003

The reaction between silicon atoms and dimethyl ether (6) has been studied in an argon matrix at 10 K and in solid dimethyl ether (6) at temperatures up to 80 K. In the initial step, a triplet n‐adductT‐5is formed between a silicon atom and6. The next step needs photochemical activation. Depending on the relative dimethyl ether/argon ratio, the photoproduct is either dimethylsilanone (1) or singlet methoxymethylsilylene (S‐2), which, in the presence of an excess of6, exists as a dimethyl ether complex8of silyleneS‐2.Longer irradiation transforms dimethyl ether addition compoundsS‐8‐t/S‐8‐cinto dimethoxydimethylsilane (7). If irradiation is applied directly during cocondensation of silicon atoms with6, the only detectable products are8and7. Upon further irradiation of the pure dimethyl ether matrix, the rest of8is also photoisomerized, and dimethoxydimethylsilane (7) is observed exclusively. The structural elucidation of all new species is based on comparison of the experimental observations with density functional theory calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Some Key Experimental Features of a Modular Synthesis of Heparin‐Like Oligosaccharides
Authors: Paz José‐Luis de , Ojeda Rafael , Reichardt Niels , Martín‐Lomas Manuel
Published: August 2003

The key features of a modular n+2 strategy for a completely stereoselective synthesis of oligosaccharides containing the GlcN−IdoA repeating unit of the major sequence of heparin are presented and discussed in detail. These key features include the regio‐ and stereoselective synthesis of disaccharide building blocks and the reactivity of building blocks in the modular assembly process. The synthetic strategy, the effectiveness of which has previously been demonstrated by the total synthesis of four hexasaccharides and two octasaccharides, allows the size and the charge distribution of the target oligosaccharide fragments to be controlled. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003
Synthesis and Structural Characterization of PNA‐DNA Quadruplex‐Forming Chimeras
Authors: Esposito Veronica , Randazzo Antonio , Messere Anna , Galeone Aldo , Petraccone Luigi , Giancola Concetta , Piccialli Gennaro , Mayol Luciano
Published: August 2003

The synthesis and structural characterization of four PNA‐DNA chimeras − 5′TGGG3′‐t (C1), 5′TGG3′‐gt (C2), t‐5′GGGT3′ (C3) and tg‐5′GGT3′ (C4), where lower and upper case letters indicate PNA and DNA residues, respectively − are reported. The oligomers were synthesized through the use of commercially available Bhoc/Fmoc PNA monomers and 3′‐ or 5′‐phosphoramidite nucleosides as building blocks. All the molecules were studied by 1H NMR, CD and UV spectroscopy and by molecular modelling. The CD spectra and NMR spectroscopic data of C1 and C3 are typical of quadruplexes involving four parallel strands. Moreover, the UV melting profiles indicate that their thermal stabilities are quite similar to that observed for the reference quadruplex [d(TGGGT)]4. The 1H NMR spectra of C2 and C4 show that these oligomers are not able to fold into a single, well defined species. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Oligo(1,4‐phenylenepyrazole‐3,5‐diyl)s
Authors: Meier Herbert , Hormaza Angelina
Published: August 2003

The bifunctional nucleophile methylhydrazine reacts in an alkaline medium in a regioselective mode with chalcones to yield 2‐pyrazolines, which can be oxidized by DDQ to the corresponding 1H‐pyrazoles. From oligo(chalcone)s this reaction yields cross‐conjugated compounds with an alternating sequence of 1,4‐disubstituted benzene rings and 3,5‐disubstituted 1H‐pyrazole rings. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Highly Enantioselective Rhodium‐Catalyzed Hydrogenation of 2‐(2‐Methoxy‐2‐oxoethyl)acrylic Acid − A Convenient Access of Enantiomerically Pure Isoprenoid Building Blocks
Authors: Ostermeier Markus , Brunner Bernhard , Korff Christian , Helmchen Günter
Published: August 2003

Asymmetric catalytic hydrogenation of 2‐(2‐methoxy‐2‐oxoethyl)acrylic acid (5) to give (2S)‐4‐methoxy‐2‐methyl‐4‐oxobutanoic acid [(S)‐6] was studied. An enantiomeric excess of 99.7% ee was achieved with a catalyst formed in situ from [Rh(COD)2]BF4 and the chiral phosphite L2 in 1,2‐dichloroethane as solvent. In addition, enzyme‐catalyzed semi‐saponification of dimethyl 2‐methylsuccinate was investigated. Mono ester (S)‐6 was transformed into a few compounds which can serve as C5‐building blocks in natural product syntheses. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)