Structural Mapping of a Chaperone–Substrate Interaction Surface

NMR spectroscopy is used to detect site‐specific intermolecular short‐range contacts in a membrane–protein–chaperone complex. This is achieved by an “orthogonal” isotope‐labeling scheme that permits the unambiguous detection of intermolecular NOEs between the well‐folded chaperone and the unfolded substrate ensemble. The residues involved in these contacts are part of the chaperone–substrate contact interface. The approach is demonstrated for the 70 kDa bacterial Skp‐tOmpA complex.     

Incorporation of Tellurocysteine into Glutathione Transferase Generates High Glutathione Peroxidase Efficiency

A rival to native peroxidase! An existing binding site for glutathione was combined with the catalytic residue tellurocysteine by using an auxotrophic expression system to create an engineered enzyme that functions as a glutathione peroxidase from the scaffold of a glutathione transferase (see picture). The catalytic activity of the telluroenzyme in the reduction of hydroperoxides by glutathione is comparable to that of native glutathione peroxidase.

     

Dispirofluorene-indenofluorene (DSFIF): synthesis, electrochemical, and optical properties of a promising new family of luminescent materials

[reaction: see text] A series of new dispiro[fluorene-9',6,9' ',12-indeno[1,2b]fluorenes] (DSFIFs) that combine indenofluorene (IF) and spirobifluorene (SBF) architectural specificities have been prepared. Their anodic oxidations lead to the formation of nonsoluble transparent polymers. The photophysical and electrochemical properties of these new molecules have been evaluated for further blue OLED applications.     

Stereoselective synthesis of fluorinated 1,3-cis-diaminocyclopentanes

Several fluorinated 1,3-diaminocyclopentanes, previously reported to be useful RNA structural probes, can be prepared in a diastereoselective manner from a single bicyclic hydrazine precursor, in 3 to 9 steps.     

Higher‐order discontinuous Galerkin method for pyramidal elements using orthogonal bases

We study finite elements of arbitrarily high‐order defined on pyramids for discontinuous Galerkin methods. We propose a new family of high‐order pyramidal finite elements using orthogonal basis functions which can be used in hybrid meshes including hexahedra, tetrahedra, wedges, and pyramids. We perform a comparison between these orthogonal functions and nodal functions for affine and non‐affine elements. Different strategies for the inversion of the mass matrix are also considered and discussed. Numerical experiments are conducted for the three dimensional Maxwell's equations. © 2012 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2013     

Betulin,a Newly Characterized Compound in Acacia auriculiformis Bark,Is a Multi-Target Protein Kinase Inhibitor

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from Acacia auriculiformis stem bark. Column chromatography and NMR spectroscopy were used to purify and characterize betulin from an ethyl acetate soluble fraction of acacia bark. Betulin, a known inducer of apoptosis, was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1ε (CK1ε), glycogen synthase kinase 3α/β (GSK-3 α/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6), and vascular endothelial growth factor receptor 2 kinase (VEGFR2) with activities in the micromolar range for each. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to investigate its putative use as an anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway, with activity similar to that of imatinib mesylate, a known ABL1 kinase inhibitor. The interaction of betulin and ABL1 was studied by molecular docking, revealing an interaction of the inhibitor with the ABL1 ATP binding pocket. Together, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and to potential treatments for leukemia.