Structural basis for thrombin activation of a protease-activated receptor: inhibition of intramolecular liganding

Protease-activated G protein-coupled receptors (PAR1-4) are tethered-ligand receptors that are activated by proteolytic cleavage of the extracellular domain (exodomain) of the receptor. PAR1, the prototypic member of the PAR family, is the high-affinity thrombin receptor of platelets and vascular endothelium and plays a critical role in blood coagulation, thrombosis, and inflammation. Here, we describe the solution structure of the thrombin-cleaved exodomain of PAR1. The side chains of a hydrophobic hirudin-like (Hir) sequence and adjacent anionic motif project into solution. Docking of the exodomain Hir sequence to exosite I of thrombin reveals that the tethered ligand in the cleaved exodomain bends away from thrombin, leaving its active site available to another large macromolecular substrate. The N-terminal ligand is longer than anticipated and forms an intramolecular complex with a region located in the C terminus of the exodomain. Mutational analysis confirmed that this C-terminal region is a ligand binding site for both intra- and intermolecular ligands. A lipidated-ligand binding site peptide was found to be an effective inhibitor of thrombin-induced platelet aggregation.     

Distribution of fallout radionuclides through soil surface layer

The distribution of¹³⁷Cs through soil layers has been investigated by field sampling. The investigation deals with¹³⁷Cs concentration found after the Chernobyl accident. The relationship between important soil characteristics, total precipitation and cesium distribution are analyzed. Cesium is strongly sorbed in the top soil layer and its migration downward is limited. Measurements performed over a 3-year period revealed that approximately 20–38 per cent of total¹³⁷Cs is located in the upper soil layer.     

Structural analysis of the conformational flexibility of tris(pyrazolyl)borate ligands and their analogues

Database analysis and molecular mechanics were used to determine the conformational flexibility of tridentate scorpionate ligands. The tris(pyrazolyl)methane and tris(pyrazolyl)borate ligands act like molecular vises, opening their tripodal structure for larger metals and closing around smaller metal ions. Tris(3-tert-butylpyrazolyl)methane has significant preference for larger metal ions than its unsubstituted parent compound. Tris(pyrazolyl)methanes and tris(pyrazolyl)borates have similar conformational flexibilities. Placing sterically hindered groups on the central carbon or boron has only a minor effect on the geometry of the tris(pyrazolyl)methanes and tris(pyrazolyl)borates. However, it does influence the flexibility of the ligands, particularly when they have to open far from their ideal geometry, which commonly occurs.     

Stereocontrol in cycloadditions of (1Z,4R*,5R*)-1-arylmethylidene-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines

Cycloadditions of (1Z,4R*,5R*)-4-benzoylamino-5-phenylpyrazolidin-3-on-1-azomethine imines to olefinic dipolarophiles were studied. Stereochemistry of cycloadditions to azomethine imines 3 was found to be controlled by stereodirecting phenyl group at position 3, as well as by the ortho-substituents at the aromatic ring at position 1′. The structures of dipoles and products were confirmed by NMR and X-ray diffraction.     

Functionalization of 2,3,4,5-Tetrahydro-1,5-benzodiazepin-2(1 H)-ones by Electrophilic Aromatic Substitution

Highly substituted, novel, 8- and 9-nitro-2,3,4,5-tetrahydro-1,5-benzodiazepin-2(1H)-ones were obtained by direct nitration of the 7-bromo-5-trifluoroacetyl (or formyl)-substituted tetrahydrobenzodiazepinones. Alkaline and acidic hydrolysis of the novel mononitro derivatives was examined. Semiempirical AM1 calculations of aromatic substituents orientation in the nitration products are presented.     

Study of flame-retardant finishing of cellulose fibres: Organic–inorganic hybrid versus conventional organophosphonate

The aim of this study was to introduce a non-formaldehyde inorganic–organic hybrid sol–gel flame-retardant precursor (SiOP) containing phosphorous, nitrogen, and silicon and to compare its functional properties with those of the conventional formaldehyde-containing organic flame-retardant agent, organophosphonate (OP). SiOP was used at concentrations of 2%, 4%, and 8%, and OP was used at a concentration of 200 g/dm³. Both agents were applied to 100% cotton (CO) woven fabric by the pad-dry-cure method under the appropriate conditions. The presence of the SiOP and OP coatings on the CO fabric was confirmed by scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier-transform infrared spectroscopy. The results of the vertical tests of flammability and the thermogravimetric analyses showed that the presence of the SiOP coating changed the thermal degradation pathway of the CO fabric and resulted in an increase in the thermo-oxidative stability of the cellulose fibres. The thermo-oxidative stability was enhanced by the addition of higher amount of dry solids. At comparable dry solids contents, OP preserved significantly greater flame retardancy and thermo-oxidative stability than did SiOP. These results indicated that the SiOP precursor could not act as an effective alternative to the OP agent in the flame-retardant protection of CO fabric.     

Optimization Condition for Thin-Layer Identification of Bronzes after Anodic Sampling

JPC – Journal of Planar Chromatography – Modern TLC - Qualitative identification of Cu, Sn, Pb, Ni, and Fe in Cu-alloys is presented. The method involves anodic sampling of alloys,...