Indoloquinoline Ligands Favor Intercalation at Quadruplex-Duplex Interfaces

Quadruplex-duplex (Q-D) junctions are increasingly considered promising targets for medicinal and technological applications. Here, a Q-D hybrid with a hairpin-type snapback loop coaxially stacked onto the quadruplex 3’-outer tetrad was designed and employed as a target structure for the indoloquinoline ligand SYUIQ-5. NMR spectral analysis demonstrated high-affinity binding of the ligand at the quadruplex-duplex interface with association constants determined by isothermal titration calorimetry of about 10⁷ M⁻¹ and large exothermicities ΔH° of −14 kcal/mol in a 120 mM K⁺ buffer at 40 °C. Determination of the ligand-bound hybrid structure revealed intercalation of SYUIQ-5 between 3’-outer tetrad and the neighboring CG base pair, maximizing π–π stacking as well as electrostatic interactions with guanine carbonyl groups in close vicinity to the positively charged protonated quinoline nitrogen of the tetracyclic indoloquinoline. Exhibiting considerable flexibility, the SYUIQ-5 sidechain resides in the duplex minor groove. Based on comparative binding studies with the non-substituted N5-methylated indoloquinoline cryptolepine, the sidechain is suggested to confer additional affinity and to fix the alignment of the intercalated indoloquinoline aromatic core. However, selectivity for the Q-D junction mostly relies on the geometry and charge distribution of the indoloquinoline ring system. The presented results are expected to provide valuable guidelines for the design of ligands specifically targeting Q-D interfaces.     

On-shell improved lattice gauge theories

By means of a spectrum conserving transformation, we show that one of the 3 coefficients in Symanzik's improved action can be chosen freely, if only spectral quantities (masses of stable particles, heavy quark potential etc.) are to be improved. In perturbation theory, the other 2 coefficients are however completely determined and their values are obtained to lowest order.Heisenberg foundation fellow     

Substituent effects of phthalimide‐based nucleoside analogs on binding a CG Watson–Crick base pair

Five differently substituted phthalimide nucleosides were studied by NMR spectroscopic techniques for their ability to recognize and bind a cytosine–guanosine (CG) Watson–Crick base pair in CD₂Cl₂. Whereas only rather weak binding was observed for analogs with an amino, acetamido, or benzamido substituent, strong binding was observed with the analogs carrying an ureido and n‐butyl ureido residue. 2D NOE measurements at low temperatures confirm the proposed binding mode for the high‐affinity ligands but indicate binding interactions for the weakly bound analogs different from the expected geometry. Copyright © 2007 John Wiley & Sons, Ltd.     

Ounded Operators on Weak Hardy Spaces and Applications

The atomic decomposition of weak Hardy spaces consisting of Vilenkin martingales is formulated. Some sufficient conditions for a sublinear operator T to be bounded from the weak Hardy space wHp to the weak wLp space are given. As applications a weak version of the Hardy-Littlewood inequality is obtained and it is shown that the maximal operator of the Cesàro means of a Vilenkin-Fourier series is bounded from wHp to wLp and is of weak type (1, 1). This yields that the Cesàro means of a function f L1 converge a.e. to the function in question, provided that the Vilenkin system is bounded.     

Maßanalyse und Katalyse

The application of automatic titration instruments for volumetric determinations using catalytic indicator reactions is described. Examples for a photometric (Mn²⁺ with EDTA), potentiometric (Hg²⁺ and Ag⁺ with KI, I^? with Hg²⁺) and biamperometric (Cu²⁺ with EDTA) regulation of the automatic titrator are given. In some of these methods, contrary to the usual way, it is the inhibitor which serves as a titrant (“titration with the brake”) and not the catalyst.     

Kinetische bestimmung von molybdän unter verwendung eines potentiostaten

A kinetic method is described for the determination of molybdenum by its catalytic effect on the peroxide-iodide reaction. The reaction rate is kept constant by adding iodide at the same rate as it is being consumed, the concentration being kept constant by a potentiostat. The rate of the addition of iodide is then proportional to the molybdenum concentration. The element was determined in the range 0.5-11 mug in 50 ml.     

A kinetic-catalytic method with repeated addition of one reactant — the determination of manganese, iodide, urease and cadmium

The use of a new kinetic-catalytic method with repeated addition of one reactant in the same system is described. The determination of manganese (periodate—malachite green; photometric observation), iodide (cerium(IV)—arsenic(III); potentiometric observation) and urease (hydrolytic splitting of urea; potentiometric observation) serves to illustrate the procedure.     

The rapid separation and determination of uranium(VI) by use of DEAE anion-exehange paper and the ring-oven technique

Summary A rapid method for the separation and determination of uranium(VI) is described. The separation of uranium (0.09–0.35 mg/ml) from various other metals is carried out on DEAE anion-exchange paper with ann-butanol-acetic acid-water system (111,v/v), and the determination completed by the ring oven method.

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Zusammenfassung Eine schnelle Methode zur Trennung und Bestimmung von Uran(VI) wird beschrieben. Die Trennung des Uran(VI) (0,09 bis 0,35 mg/ml) von anderen Metallionen erfolgt auf Anionenaustauscherpapier (DEAE) mit einem 1-Butanol-Essigsäure-Wasser-System (111v/v), die Bestimmung mit Hilfe der Ringofenmethode.

     

Geometry and cooperativity effects in adenosine-carboxylic acid complexes

NMR experiments and theoretical investigations were performed on hydrogen bonded complexes of specifically 1- and 7-15N-labeled adenine nucleosides with carboxylic acids. By employing a freonic solvent of CDClF2 and CDF3, NMR spectra were acquired at temperatures as low as 123 K, where the regime of slow hydrogen bond exchange is reached and several higher-order complexes were found to coexist in solution. Unlike acetic acid, chloroacetic acid forms Watson-Crick complexes with the proton largely displaced from oxygen to the nitrogen acceptor in an ion pairing structure. Calculated geometries and chemical shifts of the proton in the hydrogen bridge favorably agree with experimentally determined values if vibrational averaging and solvent effects are taken into account. The results indicate that binding a second acidic ligand at the adenine Hoogsteen site in a ternary complex weakens the hydrogen bond to the Watson-Crick bound carboxylic acid. However, substituting a second adenine nucleobase for a carboxylic acid in the trimolecular complex leads to cooperative binding at Watson-Crick and Hoogsteen faces of adenosine.     

Double indication in catalytic—kinetic analysis; Determination of iron(III), cyanide and molybdenum(VI)

The reactions in catalytic—kinetic methods are followed simultaneously with two independent indication systems. The information delivered by the two indication methods can be used alone or in combination for the determination of the catalyst or the inhibitor. The following examples illustrate the method: the determination of iron(III) by its catalytic action on the decomposition of hydrogen peroxide (thermometric and biamperometric indication)in the range 10–100 ng Fe/6 ml; the determination of cyanide which inhibits the catalytic activity of copper on the decomposition of hydrogen peroxide thermometric and biamperometric indication) in the range 2–60 μg CN^-/7 ml; and the determination of molybdenum based on the Landolt-type system iodide—bromate— ascorbic acid (thermometric and photometric indication) in the range 0.8–40 μg Mo/8 ml.