Induction of a remarkable conformational change in a human telomeric sequence by the binding of naphthyridine dimer: inhibition of the elongation of a telomeric repeat by telomerase

The binding of a dimeric form of the 2-amino-1,8-naphthyridine derivative (naphthyridine dimer) to a human telomeric sequence, TTAGGG, was investigated by UV melting, CD spectra, and CSI-MS measurements. Both the 9-mer d(TTAGGGTTA) and the 15-mer d(TTAGGGTTAGGGTTA) showed apparent melting temperatures (T(m)) of 45.6 and 63.6 degrees C, respectively, in the presence of naphthyridine dimer (30 microM) in sodium cacodylate buffer (50 mM, pH 7.0) containing 100 mM NaCl. The CD spectra at 235 and 255 nm of the 9-mer increased in intensity accompanied with strong induced CDs at 285 and 340 nm upon complex formation with naphthyridine dimer. UV titration of the binding of naphthyridine dimer to the 9-mer at 320 nm showed a hypochromism of the spectra. A Scatchard plot of the data showed the presence of multiple binding sites with different association constants. Cold spray ionization mass spectrometry of the complex between naphthyridine dimer and the 9-mer clearly showed that one to three molecules of the ligand bound to the dimer duplex of the 9-mer. Telomeric repeat elongation assay showed that the binding of naphthyridine dimer to the telomeric sequence inhibits the elongation of the sequence by telomerase.     

Efficiently Synthesizing Lacto-Ganglio-Series Gangliosides by Using a Glucosyl Ceramide Cassette Approach: The Total Synthesis of Ganglioside X2

The first total synthesis of the hybrid ganglioside X2, which consisted of a highly branched octasaccharide and ceramide moieties, was accomplished by using a glucosyl ceramide cassette approach. With a disaccharyl donor, the heptasaccharide could not be constructed by glycosylation of the C4 hydroxy group of galactose at the reducing end of the pentasaccharide. In contrast, through an alternative approach with two branched glycan units, a GM2-core trisaccharide, and a lacto-ganglio tetrasaccharide, the heptasaccharyl donor could be prepared and subsequently joined with a glucosyl ceramide cassette to afford the protected ganglioside, X2. Finally, global deprotection completed the synthesis, thus affording the pure ganglioside X2.     

Laboratory Microwave Spectroscopy of Interstellar Molecules

Abstract

Modern radio astronomy has revealed that various kinds of molecules exist in ther very cold region between stars: interstellar space. An electromagnetic wave with a wavelength of a few centimeters to 1 mm corresponds in energy to a few to ten degrees of Kelvin. A molecule having its spectrum in this energy region provides us with valuable information about the low-energy environment where the molecule exists. New information provided by radio astronomy has rarely been     

Application of DEM modified with enlarged particle model to simulation of bead motion in a bead mill

We applied the discrete element method （DEM） of simulation modified by an enlarged particle model to simulate bead motion in a large bead mill. The stainless-steel bead mill has inner diameter of 102 mm and mill length of 198 mm. The bead diameter and filling ratio were fixed respectively at 0.5 mm and 85%. The agitator rotational speed was changed from 1863 to 3261 rpm. The bead motion was monitored experimentally using a high-speed video camera through a transparent mill body. For the simulation, enlarged particle sizes were set as 3-6 mm in diameter. With the DEM modified by the enlarged particle model, the motion of enlarged particles in a mill was simulated.The velocity data of the simulated enlarged particles were compared with those obtained in the experiment. The simulated velocity of the enlarged particles depends on the virtual frictional coefficient in the DEM model. The optimized value of the virtual frictional coefficient can be determined by considering the accumulated mean value. Results show that the velocity of the enlarged particles simulated increases with an increase in the optimum virtual frictional coefficient, but the simulated velocity agrees well with that determined experimentally by optimizing the virtual frictional coefficient in the simulation. The computing time in the simulation decreases with increased particle size.     

Defect-effects on the photoluminescence of ZrO2 bulk,film and nanocrystals

The photoluminescence (PL) properties of ZrO₂ have been measured at different temperatures between 7 and 300 K, using various kinds of ZrO₂ specimens: bulk crystal melt-grown by a large solar furnace, thermally oxidized zirconium plate (ZrO₂ film crystal on Zr ) and nanocrystals (surface area: 35–45m²/g, diameter: 20–30 nm). The results clarify the deep and shallow energy level structures in the energy gap. Reversible UV-laser-light-induced spectral changes are observed for all of the specimens in different specimen-atmospheres (vacuum and O₂ gas). The results elucidate the defect-effects of the PL properties and the PL enhancement mechanism in ZrO₂ nanocrystals.     

Efficient synthesis of an optically active tetrahydrozerumbone exhibiting a fragrance and the application of zerumbone derivatives with a medium ring structure

(R)-Tetrahydrozerumbone 2, which has a powerful balmy fragrance, contains a stereogenic carbon at the C2 position and can be easily prepared from zerumbone 1, one of the most important materials displaying an NMRDOS character. The reduction of 2 gave two diastereomers of tetrahydrozerumbol 3, and the optically active (>99%ee) alcohols were obtained by a lipase-catalyzed stereoselective transesterification of each racemic alcohol. A barrier to this development is a long reaction time (about four weeks) and the need to separate the diastereoisomers. The desired (2R)-form of 3 was efficiently obtained by a lipase-catalyzed transesterification under optimized conditions using a diastereomeric mixture of racemic 3 as the starting material without separation of the diastereomers. Using this method, the reaction of other zerumbone derivatives is greatly improved.     

A modified Ortega method to evaluate the activation energies of solid state reactions

The application of the average linear integral isoconversional method developed by Ortega for evaluating the activation energies of solid state reactions may be hindered by experimental noise and the uncertainties associated with selecting appropriate reaction segments. This paper suggests a procedure, called the modified Ortega method, which can avoid or minimize these hindrances. By applying the modified Ortega method to the kinetic analyses of both simulated and experimental data, a more consistent dependence of the activation energy on the extent of reaction conversion was found with those calculated from the modified Vyazovkin method and the Friedman method.     

Single-Round DNA Aptamer Selection by Combined Use of Capillary Electrophoresis and Next Generation Sequencing: An Aptaomics Approach for Identifying Unique Functional Protein-Binding DNA Aptamers

In DNA aptamer selection, existing methods do not discriminate aptamer sequences based on their binding affinity and function and the reproducibility of the selection is often poor, even for the selection of well-known aptamers like those that bind the commonly used model protein thrombin. In the present study, a novel single-round selection method (SR-CE selection) was developed by combining capillary electrophoresis (CE) with next generation sequencing. Using SR-CE selection, a successful semi-quantitative and semi-comprehensive aptamer selection for thrombin was demonstrated with high reproducibility for the first time. Selection rules based on dissociation equilibria and kinetics were devised to obtain families of analogous sequences. Selected sequences of the same family were shown to bind thrombin with high affinity. Furthermore, data acquired from SR-CE selection was mined by creating sub-libraries that were categorized by the functionality of the aptamers (e. g., pre-organized aptamers versus structure-induced aptamers). Using this approach, a novel fluorescent molecular recognition sensor for thrombin with nanomolar detection limits was discovered. Thus, in this proof-of-concept report, we have demonstrated the potential of a “DNA Aptaomics” approach to systematically design functional aptamers as well as to obtain high affinity aptamers.