ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

1

Unknown

Discovery of a small molecule insulin mimetic with antidiabetic activity in mice (1999)

B. Zhang ; G. Salituro ; D. Szalkowski ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 284(5416): 974-7.

add to mindlist on the mindlist

Details

Publication Date: 1999-05-13

Description: Insulin elicits a spectrum of biological responses by binding to its cell surface receptor. In a screen for small molecules that activate the human insulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was selective for insulin receptor versus insulin-like growth factor I (IGFI) receptor and other receptor tyrosine kinases. Oral administration of L-783,281 to two mouse models of diabetes resulted in significant lowering in blood glucose levels. These results demonstrate the feasibility of discovering novel insulin receptor activators that may lead to new therapies for diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, B -- Salituro, G -- Szalkowski, D -- Li, Z -- Zhang, Y -- Royo, I -- Vilella, D -- Diez, M T -- Pelaez, F -- Ruby, C -- Kendall, R L -- Mao, X -- Griffin, P -- Calaycay, J -- Zierath, J R -- Heck, J V -- Smith, R G -- Moller, D E -- New York, N.Y. -- Science. 1999 May 7;284(5416):974-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Endocrinology, Merck Research Laboratories, R80W250, Post Office Box 2000, Rahway, NJ 07065, USA. bei_zhang@merck.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320380" target="_blank"〉PubMed〈/a〉

Keywords: Adenosine Triphosphate/metabolism ; Animals ; Ascomycota/*metabolism ; Binding Sites ; Blood Glucose/metabolism ; CHO Cells ; Cricetinae ; Diabetes Mellitus, Type 2/*drug therapy ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Enzyme Activation ; Glucose Tolerance Test ; Hyperglycemia/drug therapy ; Hypoglycemic Agents/chemistry/metabolism/*pharmacology/therapeutic use ; Indoles/chemistry/metabolism/*pharmacology/therapeutic use ; Insulin/blood/metabolism/*pharmacology ; Insulin Receptor Substrate Proteins ; Mice ; Mice, Mutant Strains ; Mice, Obese ; Molecular Mimicry ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Conformation/drug effects ; Receptor, Epidermal Growth Factor/metabolism ; Receptor, IGF Type 1/metabolism ; Receptor, Insulin/chemistry/*metabolism ; Signal Transduction

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

PAPER CURRENT

S·F·X

Fulltext

2

Electronic Resource

Mutants of a lovastatin-hyperproducingAspergillus terreus deficient in the production of sulochrin (1991)

Vinci, V. A. ; Hoerner, T. D. ; Coffman, A. D. ; [et al.]

Springer

Journal of industrial microbiology and biotechnology 8 (1991), S. 113-119

add to mindlist on the mindlist

Details

ISSN: 1476-5535

Keywords: Microtiter fermentation ; Lovastatin ; Polyketide ; Strain improvement ; Screening

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: Summary A lovastatin-hyperproducing culture ofAspergillus terreus was shown to produce several co-metabolites extracted from whole broth. The predominant co-metabolite was the benzophenone, sulochrin, reported to arise from a polyketide biosynthetic pathway. This compound was targeted for elimination by classical mutagenesis and screening. A surface culture method employing microtiter, plates was used to ferment mutants for the primary screen. Qualitative determinations of lovastatin and sulochrin production were achieved by high-performance thin-layer chromatography. A mutant, strain AH6, which produced lovastatin titers equivalent to the parent culture and no detectable sulochrin was isolated. In addition, a lovastatin-hyperproducing mutant designated CB4 was capable of producing 16% more lovastatin and 30% less sulochrin than the parent culture in shake flask fermentations. In a pilot-scale 250-gallon fermentation, strain CB4 gave a 20% increase in lovastatin titer while producing 83% less sulochrin than the parent culture.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF01578762

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

3

Electronic Resource

Interspecies Scaling of Bosentan, A New Endothelin Receptor Antagonist and Integration of in Vitro Data into Allometric Scaling (1996)

Lave, Thierry ; Coassolo, Philippe ; Ubeaud, Geneviève ; [et al.]

Springer

Pharmaceutical research 13 (1996), S. 97-101

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics ; clearance ; in vitro models ; bosentan

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract Purpose. The goal of this study was to find a rational and reliable method of using animal data to predict the clearance of metabolised drugs in humans. Methods. One such approach is to use in vitro liver models (e.g. hepatocytes and microsomes) to determine the relative capacities of the various animal species and humans to metabolise the test compound. These data can then be combined with the in vivo clearances in animals, to calculate the in vivo clearance in humans using allometric scaling techniques. In this study, this approach was evaluated with a new endothelin receptor antagonist, bosentan, which is eliminated mainly through metabolism and is characterized by very large interspecies differences in clearance. Therefore, this compound provided a stringent test of our new extrapolation method for allometric scaling. Results. The results obtained with bosentan showed that adjusting the in vivo clearance in the different animal species for the relative rates of metabolism in vitro gave a far better prediction of human clearance than an empirical correcting factor (brain weight). Conclusions. This approach provided a more rational basis for predicting the clearance of metabolised compounds in humans.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1016037519116

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

4

Electronic Resource

Untersuchungen zur Phosphorylierung von Imidodiphosphorsäurederivaten (1977)

Riesel, L. ; Claussnitzer, A. ; Ruby, C. ; [et al.]

Weinheim : Wiley-Blackwell

Zeitschrift für anorganische Chemie 437 (1977), S. 275-281

add to mindlist on the mindlist

Details

ISSN: 0044-2313

Keywords: Chemistry ; Inorganic Chemistry

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Description / Table of Contents: Investigations on the Phosphorylation of Imidodiphosphoryl DerivativesDerivatives of esters and octaalkylamides of imidodiphosphoric acid, {[X2P(O)]2N}Y (X = OR, NR2; Y = H, Na, SiMe3, MgBr), react with phosphorus(V) chlorides exclusively under formation of O-phosphorylated products. No derivatives of nitridotriphosphoric acid are formed. O-Diethoxyphosphorylated phosphazenes, X2P(O)—N=PX2-O—P(O)(OEt)2, are obtained by using diethoxyphosphoryl chloride, (EtO)2P(O)Cl. Octaalkylamides react with PCl5 to form tetrachlorophosphonium compounds containing the PCl4 group chelate-like surrounded by the octaalkyl imidodiphosphoryl tetramide anion. The product of the reaction of octaalkyl imidodiphosphoryl tetramide sodium and POCl3 seems to have an analogous constitutions.

Notes: Derivate von Estern und Octaalkylamiden der Imidodiphosphorsäure, {[X2P(O)]2N}Y (X = OR, NR2; Y = H, Na, SiMe3, MgBr), reagieren mit Phosphor(V)-chloriden ausschließlich unter Bildung O-phosphorylierter Produkte. Es entstehen keine Derivate der Nitridotriphosphorsäure. Mit Diäthoxyphosphorylchlorid, (EtO)2P(O)Cl, bilden sich O-Diäthoxyphosphorylierte Phosphazene, X2P(O)—N=PX2-O—P(O)(OEt)2. Die Octaalkylamide reagieren mit PCl5 zu Tetrachlorophosphoniumverbindungen, in denen die PCl4-Gruppe vom Octaalkylimidodiphosphoryltetramid-Anion chelatartig umgeben ist (IV). Eine analoge Konstitution scheint das Reaktionsprodukt von Octaäthylimidodiphosphoryltetramid-Natrium mit POCl3 zu haben.

Additional Material: 2 Tab.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1002/zaac.19774370140

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

5

Electronic Resource

Ester der Imidodiphosphorsäure (1977)

Riesel, L. ; Pich, G. ; Ruby, C.

Weinheim : Wiley-Blackwell

Zeitschrift für anorganische Chemie 430 (1977), S. 227-233

add to mindlist on the mindlist

Details

ISSN: 0044-2313

Keywords: Chemistry ; Inorganic Chemistry

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Description / Table of Contents: Imidodiphosphoric Acid EstersImidodiphosphoryl tetrachloride reacts with aliphatic alcohols (C1-C3) as well as with sodium phenolate to form tetraalkylesters or tetraphenylesters of the imidodiphosphoric acid, resp. The tetraalkylesters (alkyl = methyl, ethyl, n-propyl) are also formed by reaction of trichlorphosphazene phosphoryldichloride, Cl3P=N—POCl2, with the corresponding alcohols. The purification of the esters can be reached by destillation of their silyl derivatives followed by desilylation. The esters are associated by intermolecular O…H…O hydrogen bonds.

Notes: Imidodiphosphoryltetrachlorid reagiert mit Alkanolen (C1-C3) zu den Tetraalkylestern und mit Natriumphenolat zum Tetraphenylester der Imidodiphosphorsäure. Die Tetraalkylester (Alkyl = Methyl, Äthyl, n-Propyl) werden auch bei der Umsetzung von Trichlorphosphazenphosphoryldichlorid, Cl3P=N—POCl2, mit den entsprechenden Alkoholen gebildet. Die Reinigung der Ester gelingt durch Destillation ihrer Silylderivate und deren anschließender Desilylierung. Die Ester sind über intermolekulare O … H … O-Wasserstoffbrücken assoziiert.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1002/zaac.19774300121

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

6

Electronic Resource

Zur Konstitution der Trimethylsilylderivate von Imidodiphosphorylverbindungen (1977)

Riesel, L. ; Claussnitzer, A. ; Ruby, C.

Weinheim : Wiley-Blackwell

Zeitschrift für anorganische Chemie 433 (1977), S. 200-206

add to mindlist on the mindlist

Details

ISSN: 0044-2313

Keywords: Chemistry ; Inorganic Chemistry

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Description / Table of Contents: On the Constitution of the Trimethylsilyl Derivatives of Imidodiphosphoryl CompoundsEsters and dialkylamides of the imidodiphosphoric acid react with hexamethyl-disilazane to form trimethylsilyl derivatives. 1H-, 29Si-, and 31P-NMR data show the trimethylsilyl group to be bond to oxygen with rapid reversible exchange between both phosphoryloxygen atoms.

Notes: Ester und Dialkylamide der Imidodiphosphorsäure reagieren mit Hexamethyldisilazan zu den Trimethylsilylderivaten. Aus 1H-, 29Si- und 31P-NMR-Daten folgt, daß die Trimethylsilylgruppe über Sauerstoff gebunden ist und einem schnellen reversiblen Austausch zwischen den beiden Phosphorylsauerstoffatomen unterliegt.

Additional Material: 1 Tab.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1002/zaac.19774330121

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

7

Unknown

Green rust formation controls nutrient availability in a ferruginous water column (2012)

Zegeye, A. ; Bonneville, S. ; Benning, L. ; [et al.]

In: Geology

add to mindlist on the mindlist

Details

Publication Date: 2020-02-12

Description: Iron-rich (ferruginous) conditions were a prevalent feature of the ocean throughout much of Earth's history. The nature of elemental cycling in such settings is poorly understood, however, thus hampering reconstruction of paleoenvironmental conditions during key periods in Earth evolution. This is particularly true regarding controls on nutrient bioavailability, which is intimately linked to Earth's oxygenation history. Elemental scavenging during precipitation of iron minerals exerts a major control on nutrient cycling in ferruginous basins, and the predictable nature of removal processes provides a mechanism for reconstructing ancient ocean chemistry. Such reconstructions depend, however, on precise knowledge of the iron minerals formed in the water column. Here, we combine mineralogical and geochemical analyses to demonstrate formation of the mixed-valence iron mineral, green rust, in ferruginous Lake Matano, Indonesia. Carbonated green rust (GR1), along with significant amounts of magnetite, forms below the chemocline via the reduction of ferrihydrite. Further, we show that uptake of dissolved nickel, a key micronutrient required for methanogenesis, is significantly enhanced during green rust formation, suggesting a major control on methane production in ancient ferruginous settings.

Language: English

Type: info:eu-repo/semantics/article

Permalink