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Chemical Analogue (chemical + analogue)

Distribution by Scientific Domains
Chemistry75%

Selected Abstracts

Actinide-Transition Metal Heteronuclear Ions and Their Oxides: {IrUO}+ as an Analogue to Uranyl

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 17 2006
Marta Santos
Abstract Recent theoretical calculations have shown that Ir should behave as a chemical analogue to N, with the result that IrUO+, like known NUO+, is predicted to be a stable species isoelectronic with UO22+, the uranyl dication. The target heterometallic analogue to uranyl has now been prepared by direct laser desorption/ionization of a U/Ir alloy, and by oxidation of UIr+ with N2O and C2H4O. Properties of UIr+, UPt+, and UAu+ bimetallic ions have been studied. They demonstrate direct actinide,transition metal bonding, and support the concept of "autogenic isolobality". (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source]

Dimerization effect of sucrose octasulfate on rat FGF1

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2008
N. Kulahin
Fibroblast growth factors (FGFs) constitute a family of at least 23 structurally related heparin-binding proteins that are involved in regulation of cell growth, survival, differentiation and migration. Sucrose octasulfate (SOS), a chemical analogue of heparin, has been demonstrated to activate FGF signalling pathways. The structure of rat FGF1 crystallized in the presence of SOS has been determined at 2.2,Å resolution. SOS-mediated dimerization of FGF1 was observed, which was further supported by gel-filtration experiments. The major contributors to the sulfate-binding sites in rat FGF1 are Lys113, Lys118, Arg122 and Lys128. An arginine at position 116 is a consensus residue in mammalian FGF molecules; however, it is a serine in rat FGF1. This difference may be important for SOS-mediated FGF1 dimerization in rat. [source]

Parsing the Effects of Binding, Signaling, and Trafficking on the Mitogenic Potencies of Granulocyte Colony-Stimulating Factor Analogues

BIOTECHNOLOGY PROGRESS, Issue 3 2003
Casim A. Sarkar
The pharmacodynamic potency of a therapeutic cytokine interacting with a cell-surface receptor can be attributed primarily to three central properties: [1] cytokine/receptor binding affinity, [2] cytokine/receptor endocytic trafficking dynamics, and [3] cytokine/receptor signaling. Thus, engineering novel or second-generation cytokines requires an understanding of the contribution of each of these to the overall cell response. We describe here an efficient method toward this goal in demonstrated application to the clinically important cytokine granulocyte colony-stimulating factor (GCSF) with a chemical analogue and a number of genetic mutants. Using a combination of simple receptor-binding and dose-response proliferation assays we construct an appropriately scaled plot of relative mitogenic potency versus ligand concentration normalized by binding affinity. Analysis of binding and proliferation data in this manner conveniently indicates which of the cytokine properties,binding, trafficking, and/or signaling,are contributing substantially to altered potency effects. For the GCSF analogues studied here, two point mutations as well as a poly(ethylene glycol) chemical conjugate were found to have increased potencies despite comparable or slightly lower affinities, and trafficking was predicted to be the responsible mechanism. A third point mutant exhibiting comparable binding affinity but reduced potency was predicted to have largely unchanged trafficking properties. Surprisingly, another mutant possessing an order-of-magnitude weaker binding affinity displayed enhanced potency, and increased ligand half-life was predicted to be responsible for this net beneficial effect. Each of these predictions was successfully demonstrated by subsequent measurements of depletion of these five analogues from cell culture medium. Thus, for the GCSF system we find that ligand trafficking dynamics can play a major role in regulating mitogenic potency. Our results demonstrate that cytokine analogues can exhibit pharmacodynamic behaviors across a diverse spectrum of "binding-potency space" and that our analysis through normalization can efficiently elucidate hypotheses for the underlying mechanisms for further dedicated testing. We have also extended the Black-Leff model of pharmacological agonism to include trafficking effects along with binding and signaling, and this model provides a framework for parsing the effects of these factors on pharmacodynamic potency. [source]

Terpyridine,Lanthanide Complexes Respond to Fluorophosphate Containing Nerve Gas G-Agent Surrogates

CHEMISTRY - A EUROPEAN JOURNAL, Issue 18 2008
Raja Shunmugam Dr.
The significant problem of nerve gas poisoning requires new methods of detection that are sensitive and selective. A new G-type agent chemical sensor is reported that exploits terpyridine,lanthanide emission (see graphic). A detection limit of 6,ppb is obtained and the selectivity for reactive surrogates over a variety of other close chemical analogues is demonstrated. [source]