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  • 1
    ISSN: 1432-1912
    Keywords: Glucose transport ; IAPS-forskolin ; Insulin-regulated glucose transporter GLUT4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two arginine residues (RR333/334) in the conserved GRR motif located in the endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were substituted for leucine and alanine, respectively. Reconstituted glucose transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK-) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with IAPS-forskolin were not significantly affected. Exchange of a histidine residue (H337Q) previously believed to be involved in the binding of inhibitory ligands failed to affect any of the investigated parameters. These data suggest that positive charges in the GRR motif at the cytoplasmic surface of the transporter participate in the conformational changes of the carrier protein during the process of facilitated diffusion.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Key words Glucose transport ; IAPS-forskolin ; Insulin-regulated glucose transporter GLUT4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two arginine residues (RR333/334) in the conserved GRR motif located in the endofacial loop between helix 8 and 9 of the glucose transporter GLUT4 were substituted for leucine and alanine, respectively. Reconstituted glucose transport activity of the construct (GLUT4-RR333/4LA) expressed in COS-7 or LM(TK–) cells was less than 10% of that of the wild-type GLUT4. In contrast, binding of the inhibitory ligand cytochalasin B and glucose-inhibitable photolabeling with IAPS-forskolin were not significantly affected. Exchange of a histidine residue (H337Q) previously believed to be involved in the binding of inhibitory ligands failed to affect any of the investigated parameters. These data suggest that positive charges in the GRR motif at the cytoplasmic surface of the transporter participate in the conformational changes of the carrier protein during the process of facilitated diffusion.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Interpretation of the chemical and spectral (IR., UV., 1H- and 13C-NMR.) properties of the antitumor antibiotic hedamycin (C41H50N2O11) suggests that the molecule contains a methyl substituted 1-hydroxyanthraquinone nucleus, an α, β-unsaturated ketone, two sugar-like tetrahydropyran rings (4 and 8) and an aliphatic chain 2, presumably with an epoxy group (see the Scheme).
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 76 (1993), S. 563-595 
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The cyclic tetrapeptides cyclo(-Leu-Sar-Gly-), cyclo(-Val-Sar-Sar-Gly-), and cylco(-Meleu-Gly-D-Alasar-) have been synthesized from the component amino acids (BOP-Cl coupling), using the pentafluorophenyl esters for the cyclization step (42, 13, and 30% yield, respectively). Multiple deprotonation (LDA in THF/LiBr/DMPU) and addition of highly reactive electrophiles (CF3CO2D, MeI, CH2O, CH2CHCH2Br, PhCH2Br) produce cyclic tetrapeptides with additional substituents introduced diastereoselectively (70 to 〉 98% ds) in yields ranging from 20 to 90%. The C-alkylatd products are all derived from a sarcosine-enolate moiety adjacent to another N-methylamino acid. The structures of the resulting products are determined by NMR spectroscopy (DNOE and ROESY techniques) and by hydrolysis to the parent amino acids, suitable derivatization, and analysis by chromatography on a chiral GC column. It was shown in two cases that the overall yield of cyclization/alkylation to give a disubstitued cyclic tetrapeptide is higher than that of a synthesis of the same product from the corresponding amino-acid building blocks. Surprising temperature and salt effects on the yields and selectivities of the reactions of the cyclic tetrapeptide enolates are presented, and possible mechanistic interpretations are discussed.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Als Höhepunkte auf dem Gebiet der Organoelementchemie der schwereren Elemente der vierten Hauptgruppe (Gruppe 14 des Periodensystems) in den 80er Jahren gelten die Darstellung und vollständige Charakterisierung dreier Verbindungsklassen, deren Existenz bis dahin aufgrund ihrer Reaktivität für nicht möglich gehalten wurde. Hierbei handelt es sich um 1) die dreigliedrigen Ringsysteme Cyclotrisilan, -trigerman und -tristannan, 2) Moleküle mit Element-Element-Doppelbindungen einschließlich Disilen, Digermen und Distannen sowie 3) gespannte Polycyclen mit einem Gerüst aus den schwereren Elementen der 4. Hauptgruppe, z. B. Bicyclo[1.1.0]tetrasilan, Hexagermaprisman und Octasilacuban. Die meisten dieser Verbindungen sind durch sperrige Substituenten stabilisiert. Die Verbindungen ermöglichten Untersuchungen über die Veränderungen physikalischer und chemischer Eigenschaften in Abhängigkeit vom Element und den Substituenten sowie über die thermische und photochemische Reaktivität dieser Systeme, wobei zweiwertige Carben-Analoga nachgewiesen wurden. Parallel zu den experimentellen Arbeiten wurden an nahezu allen im Beitrag diskutierten Stammverbindungen Rechnungen durchgeführt. Einige Polycyclen weisen den Weg zu Verbindungen mit einer Element-Element-Dreifachbindung.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Diese Übersicht stellt neuere experimentelle Ergebnisse der Erforschung der unendlichen Geschichte der Vitamin-B12-Biosynthese vor, wobei hauptsächlich auf Arbeiten aus der Arbeitsgruppe des Autors zurückgegriffen wird. Darüber hinaus gibt sie einen persönlichen Ausblick auf die Zukunft der Naturstoff-Biosyntheseforschung. Von zentraler Bedeutung ist mittlerweile die leistungsfähige Kombination von molekularbiologischen und modernsten spektroskopischen Techniken. Jene dienen der Suche nach und der Expression von Genen, die für die Enzyme der Biosynthese codieren, diese machen die biochemischen Vorgänge im NMR-Röhrchen direkt beobachtbar. Als logische Weiterentwicklung dieser Ansätze wird die Durchführbarkeit der Eintopf-Multienzymsynthese von Naturstoffen vorgestellt. Dank der Entwicklung und Nutzung von Klonierungstechniken und der daraus resultierenden Verfügbarkeit von Enzymen für die C-C-Verknüpfung hat sich ein grundlegender Wandel im “Handwerkszeug“ des Bioorganikers vollzogen. Gleichzeitig seien aber auch die Organiker angesprochen, die sich diesen technischen Fortschritt zunutze machen wollen. Ihnen wird sich eine neue Welt natürlicher Katalysatoren erschließen, die Synthesen mit hohen Ausbeuten bei einem oftmals überraschenden, aber durchaus willkommenen Mangel an Substratspezifität versprechen. Und schließlich hoffen wir, unsere Begeisterung für diese modernen Methoden weiterzugeben, mit denen heutige wie auch künftige Generationen von Chemikern die Synthesewege der Natur zu komplexen Naturstoffen erforschen können.
    Additional Material: 24 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0570-0833
    Keywords: Bond theory ; Tin ; Germanium ; Silicon ; Strained molecules ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The organometallic chemistry of the Group 14 elements E = Si, Ge, Sn in the 1980's is highlighted by the successful construction and characterization of three systems previously thought to be too reactive to exists: (1) three-membered ring compounds including cyclotrisilane, cyclotrigermane, and cyclotristannane, (2) molecules containing E—E double bonds including disilene, digermene, and distannene, and (3) strained polycycles containing a skeleton of Group 14 elements, such as bicyclo[1.1.0]tetrasilane, hexagemaprismane, and octasilacubane. The majority of these numerous compounds now available are fully substituted with bulky ligands to suppress the reactivity intrinsic to the systems. These compounds permit examinations of (1) the variation of physical and chemical properties of a system with these elements and also with the ligands and (2) how two systems are interrelated thermally and photochemically with the intermediacy of the divalent (carbene-like) species. Theoretical calculations on virtually all of the parent compounds discussed in this review are evaluated alongside the experimental results. Some polycycles may constitute a stepping-stone on the way to compounds with a triple bond.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Angewandte Chemie International Edition in English 32 (1993), S. 1223-1243 
    ISSN: 0570-0833
    Keywords: Vitamins ; Natural products ; Biosynthesis ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: This review contains an account of recent experimental results in the continuing saga of vitamin B12 biosynthesis (largely from the author's laboratory) as well as a personal view of future directions of research in natural product biosynthesis. The emphasis is on the powerful combination of molecular biology in the search for, and the expression of, the genes encoding the biosynthetic enzymes and state-of-the-art spectroscopic techniques, in order to “view” the biochemical events as they take place in the NMR tube. As a logical development of these approaches, the feasibility of one-flask, multienzyme synthesis of natural products is addressed.[Based on a lecture given at the 27th Euchem Conference on Stereochemistry, 26th April to 4th May, 1992. Bürgenstock, Switzerland. A more explicit account of this new field has been given in “Genetically Engineered Synthesis of Complex Natural Products” (A. I. Scott Terruhedron, 1992, 48, 2559).] Implicit throughout is the profound change in the “tools of the trade” of the bioorganic chemist, thanks to the harnessing and exploitation of cloning techniques and the resultant availability of enzymes which can make carbon-carbon bonds. It is also our desire to alert organic chemists, who may wish to take advantage of these technical developments, to the fact that they will be rewarded by a new world of natural catalysts capable of high yielding, synthetic chemistry often with a surprising, but welcome, lack of substrate specificity. Finally we hope to convey our enthusiasm for the methods now at the disposal of present and future generations of chemists for studying Nature's synthetic routes to complex natural products.
    Additional Material: 23 Ill.
    Type of Medium: Electronic Resource
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