Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model

Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two series of known PLK1 inhibitors and proposed a new structure based on a hybridized 3D-QSAR model. Given the hybridized 3D-QSAR models, we designed and synthesized 4-benzyloxy-1-(2-arylaminopyridin-4-yl)-1H-pyrazole-3-carboxamides, and we inspected its inhibitory activities to identify novel PLK1 inhibitors with decent potency and selectivity.     

Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis

Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A.     

Morphological Forms of α-Alumina Particles Synthesized in 1,4-Butanediol Solution

Phase-pure, monodispersed, hexagonal plates of single-crystal α-alumina (∼ 2 μm wide and ∼0.5 μm thick) have been prepared via precipitation by treating an aluminum hydrous oxide precursor in 1,4-butanediol at 300°C under autogenous vapor pressure. Present work shows that KOH is the only reagent that precipitates an aluminum hydrous oxide precursor suitable to synthesize α-alumina in 1,4-butanediol solution. In contrast, the use of NaOH or NH₄OH as the precipitating reagent for the precursor material does not yield the alpha phase. The solution pH at which the precursor materials are precipitated is also a critical factor for the formation of α-Al₂O₃. Phase-pure α-alumina powders were also only synthesized from the aluminum hydrous oxide precursors precipitated in the pH range from 10 to 10.5. The results of X-ray diffraction and scanning electron microscopy indicate that longer reaction times promote the phase transformation from the intermediate boehmite phase to α-alumina. The complete transformation from boehmite to α-alumina requires reaction times of about 12 h.     

Rheology of poly(vinyl chloride) blends

PVC/EVA blends were studied with an extrusion plastometer in order to examine the effect of EVA on the processability of PVC. The melt flow of PVC/EVA blends containing from 4 to 30 weight percent EVA follows a simple power law between 160 and 180°C. EVA reduced the melt viscosity and enhanced processability. Blends of PVC and EVA were morphologically incompatible. The molecular weight of extruded PVC in the blends was unchanged.     

Preparation and characterization of rubber‐toughened poly(trimethylene terephthalate)/organoclay nanocomposite

Rubber‐toughened poly(trimethylene terephthalate) (PTT)–organoclay nanocomposite (RTPTTCN) was prepared by a melt mixing technique. The rubber‐toughened PTT (RTPTT) was made by blending it with ethylene propylene diene terpolymer (EPDM) and with a small amount of maleated EPDM as a compatibilizer. XRD and TEM analysis indicated that the RTPTTCN forms a partially exfoliated nanocomposite. It was observed from SEM analysis that the clay nanoparticles induced a reduction of rubber particle size in the PTT matrix. Tensile and dynamic mechanical analysis indicated that the clay nanoparticles enhance the stiffness of the RTPTT without adversely affecting its toughness. Melt rheological studies revealed that the nanocomposites exhibited strong shear thinning behavior, and a percolated network of the clay particles was formed. It was also observed from DSC that the clay nanoparticles caused an increase in the nonisothermal crystallization temperature of the PTT. POLYM. ENG. SCI., 47:863–870, 2007. © 2007 Society of Plastics Engineers     

Blends of chlorinated isotactic polypropylene with poly(ethylene-co-vinyl acetate) II. Phase studies of the miscible blends

By measuring T_g, T_m and T_c (cloud point) phase diagrams for the four miscible blends of chlorinated isotactic polypropylenes (chlorine content 39.2 (CPP-40) and 49.8 wt.-% (CP-50)) with Poly(ethylene-co-vinyl acetate)s (vinyl acetate contents 40 (EVA-40) and 45 wt.-% (EVA-45)) were investigated. The blend of CPP-50 with EVA-40 was the most compatible of the four blend pairs.     

Effect of solution properties on nanofibrous structure of electrospun poly(lactic‐co‐glycolic acid)

Electrospinning of poly(lactic‐co‐glycolic acid) (PLGA) in chloroform or 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) was investigated, focusing on its solution parameters, to develop nonwoven biodegradable nanofibrous structures for tissue engineering. PLGA nanofibers were obtained by electrospinning of 15 wt % PLGA solution and the resulting average fiber diameters were varied with the range of 270–760 nm, depending on solution property. When small amounts of benzyl triethylammonium chloride (BTEAC) was added to the PLGA/chloroform solution, the average diameter was decreased from 760 to 450 nm and the fibers were densely amounted in a straight shape. In addition, the average fiber diameter (270 nm) of nanofibers electrospun from polar HFIP solvent was much smaller than that (760 nm) of nanofibers electrospun from nonpolar chloroform solvent. Therefore, it could be concluded that conductivity or dielectric constant of the PLGA solution was a major parameter affecting the morphology and diameter of the electrospun PLGA fibers. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1214–1221, 2006     

A kinetic study on medium temperature desulfurization using a natural manganese ore

Natural manganese ores were selected as raw materials for the desulfurization sorbent because of economical efficiency and high reactivity on hydrogen sulfide. Initial reaction rates between H₂S and desulfurization sorbent of natural manganese ores were determined in a temperature range of 400-800°C using a thermobalance reactor. All reactions were first order with respect to H₂S and were expressed by the Arrhenius relation. When the sulfidation reaction was controlled by diffusion, the temperature dependence of the effective diffusivity was given by the Arrhenius equation. Activation energies and frequency factors were obtained from the product layer diffusion coefficient of various sorbents by plotting as an Arrhenius equation form. Several additives were mixed to improve the sulfidation capacity, and NiO was the best additive.     

Characterization and physical properties of polymethylphenylsilsesquioxane (PMPSQ) and hydroxyl‐functionalized polystyrene (PS–OH) hybrids

Polymethylphenylsilsesquioxane (PMPSQ–OH) and trimethylsilyl end‐blocked PMPSQ (PMPSQ–EC) were prepared. The thermal decomposition behavior of these polymers was studied by thermogravimetric analysis (TGA) and FT‐Raman spectroscopy. Hydroxyl‐functionalized polystyrene (PS–OH) was also prepared by anionic living polymerization. Thin hybrid films of PMPSQ/PS–OH with various blend ratios were obtained by spin‐coating on freshly cleaned glass. The surface morphology of the hybrid films was investigated by atomic force microscopy (AFM). In 80/20 PMPSQ/PS–OH hybrid film, the PS–OH component produced a very uniformly dispersed phase. This hybrid film contained small domains of PS–OH whose size ranged from 60 to 80 nm. As the content of PS–OH was increased, the domain morphology coarsened and phase inversion took place around 50 wt %. In the phase‐inversed system, the PMPSQ‐rich phase was uniformly distributed in the PS–OH‐rich continuous phase. In addition, temperature‐dependent dielectric properties of PMPSQ/PS–OH hybrids were investigated. Relaxation of the hybrids was observed with an increasing content of the PS–OH component due to the amorphous glass transition behavior of PS–OH. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2801–2812, 2003