Systems biology and systems chemistry: new directions for drug discovery

Improvements in drug design have historically been centered around structure-based optimization of molecule specificity for a targeted protein, in an effort to reduce unintentional binding to other proteins and off-target effects. Although the "one-to-one" drug design strategy has been successful in impairing function of targets associated with a number of diseases, recent reports of drug promiscuity, which are a potential source of adverse reactions in patients, make a case to refine the drug design strategy such that it includes an awareness of multiple interactions from both ligand and protein perspectives. Polypharmacology and chemical biology studies are amassing interaction data at rapid rates, and the integration of such data into an interpretable model requires zooming our perspective out from the single ligand-target level to the larger network-wide level. We review some of the recent developments in systems-level research for drug design and discovery, and discuss the directions that some drug design efforts are heading toward.     

The effect of viscoelasticity on the extrusion drawing in film-casting process

The governing rheological property for extrusion drawing in film-casting process is proposed in this study. The experiment of film-casting process using the high-pressure process low-density polyethylene (LDPE) was performed. The non-isothermal viscoelastic simulation of the film casting experiment was also carried out to explain the experimental results. Film width reduction phenomenon in an air gap, so-called neck-in behavior, was investigated by using the simulation of the LDPE and the model fluids exhibiting specific viscoelasticity. The neck-in phenomenon was also examined using theoretical model based on force balance and deformation type of a film. As a result, the neck-in normalized by the air gap was in good correlation with the ratio of planar to uniaxial elongational viscosity rather than the strain hardening nature of uniaxial elongational viscosity.     

Time-resolved STM studies of atom-movement effects on ionic-electronic conductor surfaces

The dynamics of photo-induced atom movements on an ionic-electronic conductor (Ag₂Se) are discussed based on measurements of surface topology by scanning tunneling spectroscopy. All changing features of the surface topologies with various photo-exposure periods were successfully measured with a scanning tunneling microscope (STM). The surface shows a curved or flat mound inside the patterned-exposure region and a wall around the edge of the mound, which change with the exposure time. This indicates that the Ag-atom movement is dependent on the position inside the photo-exposed region and on exposure periods. So, the lateral diffusion constant of Ag movement is likely not to be a constant, but a function of position and exposure period.     

Copper‐Catalyzed Borylative Allyl–Allyl Coupling Reaction

Borylative allyl–allyl coupling using allenes, bis(pinacolato)diboron, and allyl phosphates has been developed in the presence of a copper catalyst bearing an N‐heterocyclic carbene ligand. The reaction affords boryl‐substituted 1,5‐diene derivatives in good to high yields with high regioselectivity and Z selectivity.     

Novel type of heterogenized CuCl2 catalytic systems for oxidative carbonylation of methanol

A novel type of heterogenized CuCl₂ catalysts was designed for the oxidative carbonylation of methanol to dimethyl carbonate (DMC) taking account of the plausible reaction mechanism and intermediates. To prevent severe corrosion of the reaction equipment materials due to Cl^? while keeping the catalytic activity of the homogeneous CuCl₂ catalyst, we adopted, as supports (or ligands) of CuCl₂, four polymers, bearing a 2,2′-bipyridine (bpy) or pyridine (py) unit, namely, poly(2,2′-bipyridine-5,5′-diyl) (Pbpy), poly(pyridine-2,5-diyl) (Ppy), poly(N,N′-bisphenylene-2,2′-bipyridine-4,4′-dicarboxylic amide) (Bpya), and poly(4-methyl-4′-vinyl-2,2′-bipyridine) (Pvbpy), together with one chelate compound, 8-quinolinol. The catalytic activity, stability of heterogenized CuCl₂ and their corrosivities to stainless steels were examined in the liquid-phase reaction of the oxidative carbonylation of methanol. These polymer-supported catalysts showed considerable catalytic activity and stability for the DMC synthesis. In particular, the Pbpy-CuCl₂ and Ppy-CuCl₂ catalysts exhibited high DMC yields and selectivity comparable to those of the homogeneous CuCl₂ catalyst. This high activity appears to be associated with the presence of the π-conjugated system in the polymers, which affect the redox reactions of Cu involved in the catalytic reaction. All of the polymer-supported CuCl₂ catalysts could be easily recycled after filtration, and the initial catalytic activity was maintained after three times of use. The corrosive characters of the catalysts were closely related to CuCl₂ leaching from the supports, which reflects the ability of supports to coordinate Cu. These experimental results suggest that both the electronic structure and the coordination ability of the polymer supports are key factors for the development of an effective catalytic system.     

New Strategy for Controlling Biodegradability of Biodegradable Polyesters by Enzyme‐Catalyzed Surface Grafting

A novel preparation method for the core‐shell type biodegradable polyesters or biodegradable materials grafted with biodegradable polyesters was developed by alkaline surface treatment of biodegradable polyester films and subsequent enzymatic polymerization of aliphatic lactones, one example of which is shown in this study, i.e., the preparation of poly(L ‐lactide) (PLLA) film grafted with poly(ε‐caprolactone). It is revealed that only alkaline surface treatment or the combination of alkaline surface treatment and enzyme‐catalyzed grafting, the former and the latter, respectively accelerating and delaying the enzymatic degradation of PLLA, will give PLLA materials having a wide variety of biodegradability. Also, the specificity of the enzyme used for hydrolysis could be used to confirm the grafted chain species.

     

Effect of calcination temperature during preparation of Ru?Sn-alumina catalysts on the hydrogenation of carboxylic acid

The conversion of a carboxylic acid was increased to 90% with 100% selectivity to the corresponding alcohol by calcination of the catalyst precursor, Sn/alumina, of Ru–Sn/alumina in the hydrogenation of the carboxylic acid.     

Minimaxity of a preliminary test estimator for the mean of normal distribution

Summary The problem is to estimate the mean of the normal distribution under the situation where there is vague information that the mean might be equal to zero. A minimax property of the preliminary test estimator obtained by the use of AIC (Akaike information Criterion) procedure is proved under a loss function based on the Kullback-Leibler information measure.