Synthesis and triplex-forming properties of oligonucleotides containing thio-substituted C-nucleoside 4-thiopseudoisocytidine

We synthesized the 3′-phosphoramidite building block of 4-thiopseudoisocytidine (s⁴ΨiC) and incorporated it into triplex-forming oligonucleotides (TFOs). The results of thermal denaturation of triplexes incorporating s⁴ΨiC showed that s⁴ΨiC could be used as a nucleoside component of TFOs to increase the thermal stability of triplexes at pH 7.     

Correlation analyses on binding affinity of sialic acid analogues and anti-influenza drugs with human neuraminidase using ab initio MO calculations on their complex structures--LERE-QSAR analysis (IV)

We carried out full ab initio fragment molecular orbital (FMO) calculations for complexes comprising human neuraminidase-2 (hNEU2) and sialic acid analogues including anti-influenza drugs zanamivir (Relenza) and oseltamivir (Tamiflu) in order to examine the variation in the observed inhibitory activity toward hNEU2 at the atomic and electronic levels. We recently proposed the LERE (linear expression by representative energy terms)-QSAR (quantitative structure-activity relationship) procedure. LERE-QSAR analysis quantitatively revealed that the complex formation is driven by hydrogen-bonding and electrostatic interaction of hNEU2 with sialic acid analogues. The most potent inhibitory activity, that of zanamivir, is attributable to the strong electrostatic interaction of a positively charged guanidino group in zanamivir with negatively charged amino acid residues in hNEU2. After we confirmed that the variation in the observed inhibitory activity among sialic acid analogues is excellently reproducible with the LERE-QSAR equation, we examined the reason for the remarkable difference between the inhibitory potencies of oseltamivir as to hNEU2 and influenza A virus neuraminidase-1 (N1-NA). Several amino acid residues in close contact with a positively charged amino group in oseltamivir are different between hNEU2 and N1-NA. FMO-IFIE (interfragment interaction energy) analysis showed that the difference in amino acid residues causes a remarkably large difference between the overall interaction energies of oseltamivir with hNEU2 and N1-NA. The current results will be useful for the development of new anti-influenza drugs with high selectivity and without the risk of adverse side effects.     

Effects of phosphorus oxychloride and phenylphosphonic dichloride on the radical polymerization of methyl methacrylate and styrene

Effects of pentavalent phosphorus compounds on the radical polymerization of methyl methacrylate (MMA) and styrene (St) were studied. Phosphorus oxychloride (Cl₃P?O) and phenyl-phosphonic dichloride (C₆H₅Cl₂P?O) were used. Polymerization was carried out in benzene at 50°C by the standard solution method, α,α′-azobisisobutyronitrile (AIBN) being used as the initiator. In the polymerization of MMA, both phosphorus compounds increased the rate of polymerization. NMR spectral data suggested that this increasing effect was due to the complex formation between each phosphorus compound and MMA monomer. In the case of polymerization of St, NMR data also indicated the formation of a complex between the phosphorus compound and St monomer. Both phosphorus compounds showed an increasing effect for the rate of polymerization. Though these increasing effects could be explained by the complex formation, the polymerization of St in the presence of Cl₃P?O was especially found to be due to the cationic polymerization initiated simultaneously by Cl₃P?O in addition to the radical polymerization. These phosphorus compounds acted as chain-transfer agents in both polymerization systems. The parameters (Q_tr,_etr) which indicate the reactivity of a chain-transfer agent were calculated from the observed values of chain-transfer constant for both polymerization systems.     

Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment

A contact lens (CL) biosensor for in situ monitoring of tear glucose was fabricated and tested. Biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer and polydimethyl siloxane (PDMS) were employed as the biosensor material. The biosensor consists of a flexible Pt working electrode and a Ag/AgCl reference/counter electrode, which were formed by micro-electro-mechanical systems (MEMS) technique. The electrode at the sensing region was modified with glucose oxidase (GOD). The CL biosensor showed a good relationship between the output current and glucose concentration in a range of 0.03-5.0 mM, with a correlation coefficient of 0.999. The calibration range covered the reported tear glucose concentrations in normal and diabetic patients. Also, the CL biosensor was applied to a rabbit for the purpose of tear glucose monitoring. The basal tear glucose was estimated to 0.11 mM. Also, the change of tear glucose induced by the change of blood sugar level was assessed by the oral glucose tolerance test. As a result, tear glucose level increased with a delay of 10 min from blood sugar level. The result showed that the CL biosensor is expected to provide further detailed information about the relationship between dynamics of blood glucose and tear glucose.     

Importance of magnetic resistive fields in the heating of a micro-cone target irradiated by a high intensity laser

Obtaining keV ion temperatures at solid density, i.e. “warm dense matter”, in the laboratory would be of great interest to measure opacity and equations of state of matter under extremes conditions. Here we report a new means to effectively confine the energetic electrons and localize the energy deposition to a small, more uniformly heated, volume at the tip of nanofabricated micro-cone targets. This is achieved with very high contrast laser irradiation, which interacts with the cone wall to generate strong (~10 MG) localized resistive magnetic fields within the target bulk. Temperatures of up to ~200 eV are observed, with an input laser energy of 10 J. This new means has been investigated both experimentally and with Particle-In-Cell simulations.     

Surface characterization of plasma‐modified poly(ethylene terephthalate) film surfaces

Poly(ethylene terephthalate) (PET) film surfaces were modified by argon (Ar), oxygen (O₂), hydrogen (H₂), nitrogen (N₂), and ammonia (NH₃) plasmas, and the plasma‐modified PET surfaces were investigated with scanning probe microscopy, contact‐angle measurements, and X‐ray photoelectron spectroscopy to characterize the surfaces. The exposure of the PET film surfaces to the plasmas led to the etching process on the surfaces and to changes in the topography of the surfaces. The etching rate and surface roughness were closely related to what kind of plasma was used and how high the radio frequency (RF) power was that was input into the plasmas. The etching rate was in the order of O₂ plasma > H₂ plasma > N₂ plasma > Ar plasma > NH₃ plasma, and the surface roughness was in the order of NH₃ plasma > N₂ plasma > H₂ plasma > Ar plasma > O₂ plasma. Heavy etching reactions did not always lead to large increases in the surface roughness. The plasmas also led to changes in the surface properties of the PET surfaces from hydrophobic to hydrophilic; and the contact angle of water on the surfaces decreased. Modification reactions occurring on the PET surfaces depended on what plasma had been used for the modification. The O₂, Ar, H₂, and N₂ plasmas modified mainly CH₂ or phenyl rings rather than ester groups in the PET polymer chains to form C? O groups. On the other hand, the NH₃ plasma modified ester groups to form C? O groups. Aging effects of the plasma‐modified PET film surfaces continued as long as 15 days after the modification was finished. The aging effects were related to the movement of C?O groups in ester residues toward the topmost layer and to the movement of C? O groups away from the topmost layer. Such movement of the C?O groups could occur within at least 3 nm from the surface. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3727–3740, 2004     

Microreactor utilizing a vertically-aligned carbon nanotube array grown inside the channels

We have fabricated a microreactor incorporating vertically-aligned carbon nanotubes supporting Pt nanoparticles and found that the presence of aligned nanotubes significantly enhances the catalytic reaction and extends the catalyst lifetime as compared with conventional microreactors using a Pt metal film or Pt nanoparticles directly deposited on the channel walls.     

Chemical properties of 4,5‐di(ethoxycarbonyl)‐1,3‐dioxolan‐2‐yl (DECDO) as a hydroxyl protecting group of the 2′‐hydroxyl function in ribonucleosides

We describe basic chemical properties of 4,5‐di(ethoxycarbonyl)‐1,3‐dioxolan‐2‐yl (DECDO) in view of its use as a protecting group for the 2′‐hydroxyl function of ribonucleosides. The DECDO group is found to be compatible with the DMTr strategy for the currently‐used oligonucleotide synthesis. Post‐synthetic treatment with ammonia results in the conversion of this protecting group into the 4,5‐dicarbamoyl‐1,3‐dioxolan‐2‐yl (DCBDO) group which is unexpectedly more stable in aqueous acidic solution.     

Synthesis and fluorescent properties of bi- and tricyclic 4-N-carbamoyldeoxycytidine derivatives

New bi- and tricyclic deoxycytidine derivatives (dChpd, dCmpp, dCtpp, dCppp) were synthesized as analogues of a fluorescent nucleoside, dChpp, previously reported. The carbamoyl group of dChpd and the 5-position of the cytosine ring are bridged via an ethylene linker so that the modified group forms a nonplanar structure with the cytosine ring. The fluorescent study of dChpd indicated that the coplanar structure between the carbamoyl group and the cytosine ring is of importance. N-Methylation of the carbamoyl group (dCmpp) weakened the intensity of the fluorescence of dChpp, and the derivative (dCtpp), which had a thiocarbamoyl group, lost its fluorescent property. Moreover, addition of a pyrrolo-ring (dCppp) to dChpp enhanced the intensity of fluorescence, and an emission light was observed with a marked Stokes shift of 120 nm.