Chemical approaches towards unravelling kinase-mediated signalling pathways

Protein kinases control the function of about one third of cellular proteins by catalysing the transfer of the γ-phosphate group of ATP onto their substrate proteins. Protein phosphatases counter this action and also control the activation status of many kinases. Cellular responses to environmental changes, or signalling events, temporarily tilt the balance of protein phosphorylation and dephosphorylation to one side or the other. The identification of protein-kinase-substrate pairs and substrate-phosphatase pairs is critical to understanding cell function and how cells respond to environmental changes. Identification of these substrate-enzyme pairs is non-trivial, because of the structural and mechanistic conservation of the catalytic cores of protein kinases. In this tutorial review we review recent progress towards identifying protein-kinase-substrate pairs by emphasising the use of chemical genetics and purpose-designed ATP analogues that target one particular protein kinase. In addition, we discuss activity-based chemical profiling approaches, based on ATP analogues, for the detection of active kinases.     

Modifying cage structures in metal-organic polyhedral frameworks for H2 storage

Three isostructural metal-organic polyhedral cage based frameworks (denoted NOTT-113, NOTT-114 and NOTT-115) with (3,24)-connected topology have been synthesised by combining hexacarboxylate isophthalate linkers with {Cu(2)(RCOO)(4)} paddlewheels. All three frameworks have the same cuboctahedral cage structure constructed from 24 isophthalates from the ligands and 12 {Cu(2)(RCOO)(4)} paddlewheel moieties. The frameworks differ only in the functionality of the central core of the hexacarboxylate ligands with trimethylphenyl, phenylamine and triphenylamine moieties in NOTT-113, NOTT-114 and NOTT-115, respectively. Exchange of pore solvent with acetone followed by heating affords the corresponding desolvated framework materials, which show high BET surface areas of 2970, 3424 and 3394 m(2) g(-1) for NOTT-113, NOTT-114 and NOTT-115, respectively. Desolvated NOTT-113 and NOTT-114 show high total H(2) adsorption capacities of 6.7 and 6.8 wt%, respectively, at 77 K and 60 bar. Desolvated NOTT-115 has a significantly higher total H(2) uptake of 7.5 wt% under the same conditions. Analysis of the heats of adsorption (Q(st)) for H(2) reveals that with a triphenylamine moiety in the cage wall, desolvated NOTT-115 shows the highest value of Q(st) for these three materials, indicating that functionalisation of the cage walls with more aromatic rings can enhance the H(2)/framework interactions. In contrast, measurement of Q(st) reveals that the amine-substituted trisalkynylbenzene core used in NOTT-114 gives a notably lower H(2)/framework binding energy.     

Complexation between the fungicide tebuconazole and copper(II) probed by electrospray ionization mass spectrometry

Electrospray ionization mass spectrometry (ESI-MS) is used to probe the complex formation between tebuconazole (1) and copper(II) salts, which both are commonly used fungicides in agriculture. Experiments with model solutions containing 1 and CuCl(2) reveal the initial formation of the copper(II) species [(1)CuCl](+) and [(1)(2)CuCl](+) which undergo reduction to the corresponding copper(I) ions [(1)Cu](+) and [(1)(2)Cu](+) under more drastic ionization conditions in the ESI source. In additional experiments, copper/tebuconazole complexes were also detected in samples made from soil solutions of various origin and different amount of mineralization. The direct sampling of such solutions via ESI-MS is thus potentially useful for understanding of the interactions between copper(II) salts and tebuconazole in environmental samples.     

An analytical formula for pricing m-th to default swaps

The computational effort of pricing an m-th to default swap depends highly on the size n of the underlying basket. Usually, n different default times are modeled, but in fact the valuation only depends on the m-th smallest default time of this tuple. In this paper we attain an analytical formula for the distribution of this m-th default time. With the help of this distribution we simplify the valuation problem from an n-dimensional quadrature to a one-dimensional quadrature and break the curse of dimensionality. Applications of this modification are efficient pricing of m-th to default swaps, estimation of sensitivities and pricing of European max/min options.     

An improved mixed finite element based on a modified least-squares formulation for hyperelasticity

The present work deals with the solution of geometrically nonlinear elastic problems solved by the least-squares finite element method (LSFEM). The main goal is to obtain an improved performance and an accurate approximation in particular for lower-order elements. Basis for the mixed element is a first-order stress-displacement formulation resulting from a classical least-squares method. Similar to the ideas in SCHWARZ ET AL. [1] a modified weak form is derived by the introduction of an additional term controlling the stress symmetry condition. The approximation of the unknowns follows the same procedures as for a conventional least-squares method, see e.g. CAI & STARKE [2]. The proposed modified formulation is compared to recently developed classical LSFEMs, in order to show the improvement of performance and accuracy. (© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Review: the multicolored coordination chemistry of violurate anions

This review provides a comprehensive overview on the coordination chemistry of violuric acid, C₄H₃N₃O₄ (= H₃Vio), and its derivatives (e.g. 1,3-diorganovioluric acids and thiovioluric acid). The most remarkable property of these colorless compounds is the formation of brightly colored (pantochromic/polychromic) salts with colorless cations such as alkali metal and alkaline earth metal ions and organoammonium ions. These magnificent colors have fascinated chemists for more than a century. Only in recent years it has been fully recognized that the structural chemistry of violurates is rather interesting and diverse. Violurate anions are excellent building blocks for new supramolecular assemblies in the crystalline state. Various organoammonium violurates and transition metal violurate complexes have been structurally characterized through single-crystal X-ray diffraction. Highly characteristic for these structures is the formation of 1D, 2D, or 3D hydrogen-bonded assemblies in the crystalline state. This review provides a comprehensive overview on the multicolored coordination chemistry of violurate anions, with the focus being on structurally characterized species.     

Marine Algae-PLA composites as de novo alternative to porcine derived collagen membranes

Resorbable and volume-stable collagen matrices have been preferred as grafting materials for diverse clinical applications in recent years. On the other hand, there is always an existing risk of transmission of infection with the cells or the tissues of the graft in using such collagen matrices. Moreover, considering the economic aspects, there is also a need for cost-efficient alternative materials. In this sense, marine algae can be considered as alternatives since they represent vast and cheap source of potential biopolymers. This work covers a comprehensive cytocompatibility study of composite biopolymers derived from different types of marine algae.