Iterative Antimicrobial Candidate Selection from Informed D‐/L‐Peptide Dimer Libraries

Growing resistance to antibiotics, as well as newly emerging pathogens, stimulate the investigation of antimicrobial peptides (AMPs) as therapeutic agents. Here, we report a new library design concept based on a stochastic distribution of natural AMP amino acid sequences onto half‐length synthetic peptides. For these compounds, a non‐natural motif of alternating D ‐ and L ‐backbone stereochemistry of the peptide chain predisposed for β‐helix formation was explored. Synthetic D ‐/L ‐peptides with permuted half‐length sequences were delineated from a full‐length starter sequence and covalently recombined to create two‐dimensional compound arrays for antibacterial screening. Using the natural AMP magainin as a seed sequence, we identified and iteratively optimized hit compounds showing high antimicrobial activity against Gram‐positive and Gram‐negative bacteria with low hemolytic activity. Cryo‐electron microscopy characterized the membrane‐associated mechanism of action of the new D ‐/L ‐peptide antibiotics.     

Abreicherung von Flüssiggas aus Erdgas mittels Zeolithmembranen

The depletion of higher alkanes from methane is a key aspect during the conditioning of natural gases or accompanying gases. Membrane technologies could be used as alternative to energy and cost intensive purifications. Against this background the influence of membrane geometry, composition of the gas mixture as well as temperature and pressure was investigated in separation experiments for methane/n‐butane mixtures using MFI membranes.     

Harnstoffhydrolyse für die selektive katalytische Reduktion von NOx: Vergleich der Flüssig‐ und Gasphasenzersetzung

In order to reduce the NO_x concentration in car exhausts usually the selective catalytic reduction with ammonia is used. However, to avoid the transport of ammonia in vehicles urea is applied as NH₃ precursor. Controlled urea decomposition before the injection into the exhaust gas system itself may be accomplished by the use of a separate reactor. Urea decomposition to ammonia in the liquid phase under pressure in a heated reactor was compared to its decomposition in the gas phase. In the liquid phase, higher conversion rates relative to the reactor volume were realized than in the gas phase. Catalysts which showed high activity in the gas phase influenced the decomposition in the liquid phase only slightly.     

Hydrothermally Stable WO3/ZrO2–Ce0.6Zr0.4O2 Catalyst for the Selective Catalytic Reduction of NO with NH3

A new catalyst WO₃/ZrO₂–Ce_0.6Zr_0.4O₂ (15 wt % WO₃/ZrO₂:Ce_0.6Zr_0.4O₂ = 50:50) has been developed for the selective catalytic reduction of NO with NH₃. The redox component Ce_0.6Zr_0.4O₂ was dispersed on the surface of acidic WO₃/ZrO₂ by the solution combustion method showing the best NO _x reduction efficiency among the catalysts prepared by various modes of mixing of the components. The catalyst has been characterized by XRD, Raman spectroscopy and NH₃-TPD. A NO _x reduction efficiency of more than 90 % was obtained between 300 and 500 °C at α = NH_3,in/NO _x,in = 1. The catalyst showed stable NO _x reduction efficiency after hydrothermal ageing at 700 °C. Sulfur poisoning promoted the NO _x reduction efficiency at high temperatures at the expense of a reduced activity at lower temperatures, but the catalyst could be fully regenerated by heating in O₂ at 650 °C.     

Lipoxygenase Products in the Urine Correlate with Renal Function and Body Temperature but not with Acute Transplant Rejection

Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.     

An NMR‐MOUSE® for Analysis of Thin Objects

A special unilateral NMR sensor has been designed for investigations of thin samples with a thickness of less than 1 mm and of surface effects of polymers. For use with the bar‐magnet NMR‐MOUSE®, the so‐called “crazy coil” is introduced with a low penetration depth. It is a flat meander coil etched on a printed circuit board with wiggles in the conductors. The design of the new coil and FEM simulations of the B ₁ field are presented. Different applications are discussed by means of illustrative examples. They are the detection of surface damage in rubber samples, the swelling and drying of a latex membrane exposed to cyclohexane vapor mimicking a chemical sensor, and the drying of a thin sprayed adhesive layer.

Bar‐magnet NMR‐MOUSE® with crazy coil.     

Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice

Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR)) were randomized into four groups: control (Ctrl)—untreated mice administered distilled water for 28 days; Pb-exposed group (Pb)—mice administered orally an average daily dose of 80 mg/kg body weight (BW) lead (II) nitrate (Pb(NO₃)₂) during the first two weeks of the experimental protocol followed by the administration of distilled water for another two weeks; salinomycin-treated (Pb + Sal) group—Pb-exposed mice, administered an average daily dose of 16 mg/kg BW salinomycin for two weeks; deferiprone-treated (Pb + Def) group—Pb-exposed mice, administered an average daily dose of 20 mg/kg BW deferiprone for 14 days. The exposure of mice to Pb induced significant accumulation of the toxic metal in the kidneys and elicited inflammation with leukocyte infiltrations near the glomerulus. Biochemical analysis of the sera revealed that Pb significantly altered the renal function markers. Pb-induced renal toxicity was accompanied by a significant decrease in the endogenous renal concentrations of phosphorous (P), calcium (Ca), copper (Cu) and selenium (Se). In contrast to deferiprone, salinomycin significantly improved renal morphology in Pb-treated mice and decreased the Pb content by 13.62% compared to the Pb-exposed group. There was also a mild decrease in the renal endogenous concentration of magnesium (Mg) and elevation of the renal concentration of iron (Fe) in the salinomycin-treated group compared to controls. Overall, the results demonstrated that salinomycin is a more effective chelating agent for the treatment of Pb-induced alterations in renal morphology compared to deferiprone.     

New Aromatic Azapentalenes: 3H‐ and 2H‐Imidazo[1,2‐d]tetrazoles

A number of title compounds ( 3a,c,4a—c ) were prepared by cyclization of 5‐aminotetrazolium salts having ketonic substituents ( 1,2 ). The following procedures were applied: a) for 3a, 4a,b : heating of 1a, 2a,b with acetic anhydride‐ base; b) for 3c,4c : heating of 1b,2b in a buffer solution of pH 6.5 (Tschitschibabin reaction). The proclivity for ring closure was more pronounced with the salts 2 . The 6‐unsubstituted representatives 3c and 4c underwent S_E‐reactions, the 2H‐isomer 4c being slightly more reactive; this was confirmed by AM1 calculations. The nitroso product 4g exists predominantly as the valence‐isomeric nitrile oxide 6 .     

Evaluation of pathways for washing soluble solids

Filter cake washing is a purification method for particulate products in liquids. This process is mostly one step of a sequence in a solid–liquid separation process. For soluble products not only the mechanical transport mechanisms in washing but also the dissolution process of the product must be considered in order to describe the washing process appropriately. An unconsidered dissolution may cause problems and often severe product loss depending on the material properties. This paper presents several methods of soluble solids washing including filter cake washing by pressure and centrifugal forces as well as moving bed washing. The advantages and drawbacks of each method are discussed to evaluate the suitability of its technical application.     

Induction of DNA-double-strand breaks by auger electrons from 99mTc complexes with DNA-binding ligands

The potential of certain Auger electron emitting nuclides for systemic radiotherapeutic applications has recently gained much attention. In particular, the ability of several nuclides, including 111In, 125I, and 123I, to induce DNA double-strand breaks (dsb), a good indicator of cytotoxicity, has been extensively studied. However, this ability has never previously been shown experimentally for 99mTc, which, besides the well-known gamma radiation that is used for diagnostic applications, also emits an average of 1.1 conversion electrons and 4 Auger or Coster-Kronig electrons per decay. Owing to the short range of Auger electrons, the radionuclide needs to be located very close to the DNA for dsb to occur. We synthesized two cationic 99mTcI-tricarbonyl complexes with pendant DNA binders, pyrene and anthraquinone. The X-ray crystal structures of the two complexes could be elucidated. Linear dichroism and UV/Vis spectroscopy revealed that the complex with pyrene intercalates DNA with a stability constant, K, of 1.1 x 10(6) M(-1), while the analogous complex with anthraquinone interacts with DNA in a groove-binding mode and has an affinity value of K=8.9 x 10(4) M(-1). We showed with phiX174 double-stranded DNA that the corresponding 99mTc complexes induce a significant amount of dsb, whereas non-DNA-binding [TcO4]- and nonradioactive Re compounds did not. These results indicate that the Auger electron emitter 99mTc can induce dsb in DNA when decaying in its direct vicinity and this implies potential for systemic radiotherapy with 99mTc complexes.