Discovery of aminoglycoside mimetics by NMR-based screening of Escherichia coli A-site RNA

A method is described for the NMR-based screening for the discovery of aminoglycoside mimetics that bind to Escherichia coli A-site RNA. Although aminoglycosides are clinically useful, they exhibit high nephrotoxicity and ototoxicity, and their overuse has led to the development of resistance to important microbial pathogens. To identify a new series of aminoglycoside mimetics that could potentially overcome the problems associated with toxicities and resistance development observed with the aminoglycosides, we have prepared large quantities of E. coli 16 S A-site RNA and conducted an NMR-based screening of our compound library in search for small-molecule RNA binders against this RNA target. From these studies, several classes of compounds were identified as initial hits with binding affinities in the range of 70 microM to 3 mM. Lead optimization through synthetic modifications of these initial hits led to the discovery of several small-molecule aminoglycoside mimetics that are structurally very different from the known aminoglycosides. Structural models of the A-site RNA/ligand complexes were prepared and compared to the three-dimensional structures of the RNA/aminoglycoside complexes.     

Discovery of a potent,selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy

Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.     

Reaction of [Pt(NH3)4]Cl2 with NH4VO3 in an Alkaline Solution at 190°C in Autoclave

Russian Journal of General Chemistry - The reaction of [Pt(NH3)4]Cl2 with NH4VO3 in alkaline solution in an autoclave at 190°C was studied. The solid autoclave thermolysis product was...     

Thermolysis of [Pd(NH3)4]Cl2–(NH4)2Cr2O7 Mixtures in an Inert Atmosphere

Russian Journal of Physical Chemistry A - Sequential thermal transformations of a 3[Pd(NH3)4]Cl2–2(NH4)2Cr2O7 mixture (Pd : Cr molar ratio, 3 : 4) are studied via thermal analysis and mass...     

Rhenium- and ruthenium-containing catalysts for neutralization of automobile exhaust

The rhenium- and ruthenium-containing catalysts are active in the oxidation of CH _x and CO and in the reduction of NO _x . Comparative testing of catalyst samples under laboratory conditions and on an engine stand demonstrated that these catalysts outperform the known commercial catalysts in the neutralization of exhaust gas from automotive gasoline engines. It is, therefore, possible to completely replace expensive Rh and partially replace Pt and Pd with cheaper components—Re and Rh—in the manufacturing of catalytic converters.     

The three-dimensional photonic crystals coated by gold nanoparticles

We report on the fabrication of metallodielectric photonic crystals by means of interference lithography and subsequent coating by gold nanoparticles. The grating is realized in a SU-8 photoresist using a He-Cd laser of wavelength 442 nm. The use of the wavelength found within the photoresist low absorption band enables fabricating structures that are uniform in depth. Parameters of the photoresist exposure and development for obtaining a porous structure corresponding to an orthorhombic lattice are determined. Coating of photonic crystals by gold nanoparticles is realized by reduction of chloroauric acid by a number of reductants in a water solution. This research shows that the combination of interference lithography and chemical coating by metal is attractive for the fabrication of metallodielectric three-dimensionally periodic microstructures.     

Über die Natur der Anomalien der Konzentrationsabh:angigkeit der Viskosität von gefüllten Polymeren im Bereich kleiner Füllungsgraden

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