Pyrazolo[3,4-d][1,2,3]triazine DNA: synthesis and base pairing of 7-deaza-2,8-diaza-2'-deoxyadenosine

7-deaza-2,8-diaza-2'-deoxyadenosine (4) was synthesized from 8-aza-7-deaza-2'-deoxyadenosine (1) via the 1,N(6)-etheno derivative 5. Ring opening with sodium hydroxide followed by ring closure in the presence of sodium nitrite formed the tricyclic intermediate 5 from which the transiently introduced "etheno" moiety was removed with NBS. Compound 4 was converted to the phosphoramidite 11, which was employed in solid-phase oligonucleotide synthesis. Base pairing studies on 4, incorporated in a 12-mer duplex, showed that this adenine nucleoside analogue forms a strong base pair with dG but not with dT. This novel base pair is as stable as that of the canonical dA-dT pair. As a result of the absence of nitrogen-7 compound 4 is expected to form a face to face base pair with dG.     

Anodic Deposition of Iodide Ion at Silver Electrode

Anodic deposition of iodide ion on silver at 25° in aqueous (0.5 M KNO₃) and in 90% (w/w) ethanol-water (0.05 M KClO₄) solutions was studied galvanostatically. The exchange current density, transfer coefficient and the rate constants for the electrode reaction were evaluated. The experimental results revealed that the overall electrode reaction and the charge-transfer step was the same one, i.e., , which might be assumed highly reversible as reflected by the exchange current density (i) and transfer coefficient (α). The numerical values of the rate constants, and at 25° were, in aqueous solution, 1.02×10^?5 and 2.88×10^?6, and in ethanol solution, 2.88×10^?5 and 6.3×10^?6 cm sec^?1, respectively.     

Interactions of Some Amino Acids with Aqueous N,N-Dimethylacetamide Solutions at 298.15 and 308.15 K: A Volumetric Approach

The apparent molar volumes, V _φ , of glycine, L-alanine and L-serine were obtained in aqueous 0 to ∼4 mol⋅kg⁻¹ N,N-dimethylacetamide (DMA) solutions from density measurements at 298.15 and 308.15 K. The standard partial molar volume, V _φ ^o, and standard partial molar volumes of transfer, Δ_tr V _φ ^o, were determined for these amino acids. It has been shown that hydrophilic-hydrophilic interactions between charged groups of the amino acids and the —CON= group of DMA are predominant in the case of glycine and L-serine, but for L-alanine the interactions between its side group (—CH₃) and DMA are predominant. An increase in temperature increases the standard partial molar volumes but decreases the transfer volumes of the amino acids. The results have been interpreted in terms of cosphere overlap model.     

Asymmetric reduction of representative ketones with a bis-chiral oxazaborolidine system

In recent years, many optically active β-amino alcohols, mostly derived from naturally occurring α-amino acids, have been incorporated into the asymmetric synthesis as chiral auxiliaries or ligands.1 An effective asymmetric catalysts, the oxazaborolidine-borane reagents, which were originally pioneered by Itsuno and Corey,2 were generally prepared from chiral β-amino alcohols by the reaction with boric acid or formed in situ in the presence of borane. These reagents provide excellent enanti…     

Electroosmotic flow controllable coating on a capillary surface by a sol-gel process for capillary electrophoresis

A simple coating procedure employing a sol-gel process to modify the inner surface of a bare fused-silica capillary with a positively charged quaternary ammonium group is established. Scanning electron microscopic studies reveal that a smooth coating with 1 to approximately 2 microm thickness can be obtained at optimized coating conditions. With 40 mM citrate as a running electrolyte, the plot of electroosmotic flow (EOF) versus pH shows a unique three-stage EOF pattern from negative to zero and then to positive over a pH range of 2.5 to 7.0. At pH above 5.5, the direction of the EOF is from the anode to the cathode, as is the case in a bare fused-silica capillary, and the electroosmotic mobility increases as the pH increases. However, the direction of the EOF is reversed at pH below 4.0. Over the pH range of 4.0 to 5.5, zero electroosmotic mobility is obtained. Such a three-stage EOF pattern has been used to separate six aromatic acids under suppressed EOF and to separate nitrate and nitrite with the anions migrating in the same direction as the EOF. The positively charged quaternary ammonium group on the coating was also utilized to minimize the adsorption problem during the separation of five basic drugs under suppressed EOF and during the separation of four basic proteins with the cations migrate in the opposite direction as the EOF. Also, the stability and reproducibility of this column are good.     

Hyperpolarized 129Xe NMR investigation of multifunctional organic/inorganic hybrid mesoporous silica materials

An extensive study has been made on a series of multifunctional mesoporous silica materials, prepared by introducing two different organoalkoxysilanes, namely 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane (AEPTMS) and 3-cyanopropyltriethoxysilane (CPTES) during the base-catalyzed condensation of tetraethoxysilane (TEOS), using the variable-temperature (VT) hyperpolarized (HP) 129Xe NMR technique. VT HP-129Xe NMR chemical shift measurements of adsorbed xenon revealed that surface properties as well as functionality of these AEP/CP-functionalized microparticles (MP) could be controlled by varying the AEPTMS/CPTES ratio in the starting solution during synthesis. Additional chemical shift contribution due to Xe-moiety interactions was observed for monofunctional AEP-MP and CP-MP as well as for bifunctional AEP/CP-MP samples. In particular, unlike CP-MP that has a shorter organic backbone on the silica surface, the amino groups in the AEP chain tends to interact with the silanol groups on the silica surface causing backbone bending and hence formation of secondary pores in AEP-MP, as indicated by additional shoulder peak at lower field in the room-temperature 129Xe NMR spectrum. The exchange processes of xenon in different adsorption regions were also verified by 2D EXSY HP-129Xe NMR spectroscopy. It is also found that subsequent removal of functional moieties by calcination treatment tends to result in a more severe surface roughness on the pore walls in bifunctional samples compared to monofunctional ones. The effect of hydrophobicity/hydrophilicity of the organoalkoxysilanes on the formation, pore structure and surface property of these functionalized mesoporous silica materials are also discussed.     

Molecular dynamics on a distributed-memory multiprocessor

Dynamics simulations of molecular systems are notoriously computationally intensive. Using parallel computers for these simulations is important for reducing their turnaround time. In this article we describe a parallelization of the simulation program CHARMM for the Intel iPSC/860, a distributed memory multiprocessor. In the parallelization, the computational work is partitioned among the processors for core calculations including the calculation of forces, the integration of equations of motion, the correction of atomic coordinates by constraint, and the generation and update of data structures used to compute nonbonded interactions. Processors coordinate their activity using synchronous communication to exchange data values. Key data structures used are partitioned among the processors in nearly equal pieces, reducing the memory requirement per node and making it possible to simulate larger molecular systems. We examine the effectiveness of the parallelization in the context of a case study of a realistic molecular system. While effective speedup was achieved for many of the dynamics calculations, other calculations fared less well due to growing communication costs for exchanging data among processors. The strategies we used are applicable to parallelization of similar molecular mechanics and dynamics programs for distributed memory multiprocessors. © 1992 by John Wiley & Sons, Inc.     

Fluorescence immunoassay of alpha-fetoprotein with iron(III) tetrasulfonatophthalocyanine as a mimetic enzyme labeling reagent

A new fluorimetric immunoassay for alpha-fetoprotein (AFP) has been developed using a novel promising mimetic peroxidase, iron(III) tetrasulfonatophthalocyanine (FeTSPc), as a labeling reagent to catalyze the fluorescence reaction of P- hydroxyphenylacetic acid (P-HPA) and hydrogen peroxide (H2O2). In the competitive immunoassay, anti-AFP antibody was coated on a 96-well plate (polystyrene) and a constant amount of FeTSPc-labeled AFP and a known amount of test solution were added. Non-labeled and FeTSPc-labeled AFP compete for binding to the plate-bound antibody. After the immunoreaction, the immunochemically adsorbed FeTSPc-AFP conjugate moiety was determined by measuring the fluorescence produced in a solution containing P-HPA and H2O2. AFP can be determined in the concentration range of 1-300 ng mL(-1) with a detection limit of 0.5 ng mL(-1).     

Systems-based design of bi-ligand inhibitors of oxidoreductases: filling the chemical proteomic toolbox

Genomics-driven growth in the number of enzymes of unknown function has created a need for better strategies to characterize them. Since enzyme inhibitors have traditionally served this purpose, we present here an efficient systems-based inhibitor design strategy, enabled by bioinformatic and NMR structural developments. First, we parse the oxidoreductase gene family into structural subfamilies termed pharmacofamilies, which share pharmacophore features in their cofactor binding sites. Then we identify a ligand for this site and use NMR-based binding site mapping (NMR SOLVE) to determine where to extend a combinatorial library, such that diversity elements are directed into the adjacent substrate site. The cofactor mimic is reused in the library in a manner that parallels the reuse of cofactor domains in the oxidoreductase gene family. A library designed in this manner yielded specific inhibitors for multiple oxidoreductases.