• Bulletin of the Korean Chemical Society
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• v.28 no.6
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• pp.947-952
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• 2007

Mycobacterium tuberculosis is a pathogen responsible for 2-3 million deaths every year worldwide. The emergence of drug-resistant and multidrug-resistant tuberculosis has increased the need to identify new antituberculosis targets. Acetohydroxy acid synthase, (AHAS, EC 2.2.1.6), an enzyme involved in branched-chain amino acid synthesis, has recently been identified as a potential anti-tuberculosis target. To assist in the search for new inhibitors and “receptor-based” design of effective inhibitors of tubercular AHAS (TbAHAS), we constructed four different structural models of TbAHAS and used one of the models as a target for virtual screening of potential inhibitors. The quality of each model was assessed stereochemically by PROCHECK and found to be reliable. Up to 89% of the amino acid residues in the structural models were located in the most favored regions of the Ramachandran plot, which indicates that the conformation of each residue in the models is good. In the models, residues at the herbicide-binding site were highly conserved across 39 AHAS sequences. The binding mode of TbAHAS with a sulfonylurea herbicide was characterized by 32 hydrophobic interactions, the majority of which were contributed by residue Trp516. The model based on the highest resolution X-ray structure of yeast AHAS was used as the target for virtual screening of a chemical database containing 8300 molecules with a heterocyclic ring. We developed a short list of molecules that were predicted to bind with high scores to TbAHAS in a conformation similar to that of sulfonylurea derivatives. Five sulfonylurea herbicides that were calculated to efficiently bind TbAHAS were experimentally verified and found to inhibit enzyme activity at micromolar concentrations. The data suggest that this time-saving and costeffective computational approach can be used to discover new TbAHAS inhibitors. The list of chemicals studied in this work is supplied to facilitate independent experimental verification of the computational approach.

• Clean Technology
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• v.18 no.1
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• pp.57-62
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• 2012

Aqueous poly (vinyl alcohol) (PVA) solution was modified by using hydrophobic vinyltriethoxysilane (VTEOS) and then adding different amounts of poly (acrylic acid) (PAA) to the resulting solution. Thermal and mechanical properties, contact angle, water vapor transmission rate (MVTR) and oxygen gas transmission rate ($O_2TR$) of the film samples fabricated by these solutions were investigated. The glass transition temperature (Tg) of the VTEOS-modified films was sightly increased and the value remained unchanged according to the amount of PAA. The tensile strength of the VTEOS-modified films was found to be 9.48~10.72 $kg/mm^2$ which showed no significant difference compared with that of PVA. The film prepared with VTEOS-modified PVA/PAA (= 90/10), of which the swelling and solubility were measured to be 198% and 0%, respectively, showed improved water-resistance. The MVTR and $O_2TR$ for the PET film (thickness 50 ${\mu}m$) coated with VTEOS-modified PVA/PAA (= 90/10) film (thickness 2.5 ${\mu}m$) were measured to be 11.04 $g/m^2/day$ and 3.1 $cc/m^2/day$, respectively.

• Polymer(Korea)
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• v.29 no.5
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• pp.440-444
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• 2005

An increase in the surface area of drugs by reducing particle sizes from microns to nanometers has been known as an efficient method to improve the bioavailability of water-insoluble drugs. To prevent drug nanoparticles from aggregation during the processes of drug formulation, a limited number of pharmaceutical inactive ingredients such as hydroxypropyl cellulose has been employed as stabilizers or dispersants. In this study, copolymers of hydrophilic and hydrophobic amino acids were synthesized by the ring opening polymerization of their N-carboxyanhydride monomers and evaluated as novel candidates to stabilize the nanoparticles of a water insoluble drug, naproxen. Naproxen nanoparticles stabilized by synthesized amino acid copolymers were successfully prepared in the size of $200\~500nm$ in 60 min by a wet comminution process. Particle size analysis showed that the effective stabilization performance of copolymers required the hydrophobic moiety content to be higher than $10 mol\%$. However, the molecular weight and morphology of copolymers was not the critical parameters in determining the particle size reduction. Their particle size was found to be stable up to 14 days without significant aggregation.

• Macromolecular Research
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• v.8 no.1
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• pp.26-33
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• 2000

A series of pH/temperature sensitive polymers were synthesized by copolymerizing N-isopro-pyl acrylamide(NIPAAm) and acrylic acid(AAc) . The influence of polyelectrolyte between poly(allyl amine) (PAA) and poly(L-lysine)(PLL) on the lower critical solution temperature(LCST) of pH/temperature sensitive polymer was compared in the range of pH 2∼12. The LCST of PNIPAAm/water in aqueous poly(NIPAAm-co-AAc) solution was determined by cloud point measurements. A polyelectrolyte complex was prepared by mixing poly(NIPAAm-co-AAc) with poly(allyl amine) (PAA) or poly(L-lysine) (PLL) solutions as anionic and cationic polyelectrolytes, respectively. The effect of polyelectrolyte complex formation on the conformation of PLL was studied as a function of temperature by means of circular dichroism(CD). The cloud points of PNIPAAm in the aqueous copolymers solutions were stongly affected by pH, the presence of polyelectrolyte solute, AAc content, and charge density. The polyelectrolyte complex was formed at neutral condition. The influence of more hydrophobic PLL as a polyelectrolyte on the cloud point of PNIPAAm in the aqueous copolymer solution was stronger than that of poly(allyl amine)(PAA). Although polymer-polymer complex was formed between poly(NIPAAm-co-AAc) and PLL, the conformational change of PLL did not occur due to steric hinderance of bulky N-isopropyl groups of PNIPAAm.

• BMB Reports
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• v.46 no.5
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• pp.276-281
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• 2013

In this study, we aimed to compare the morphogenetic and neuronal characteristics between monolayer cells and spheroids. For this purpose, we established spheroid formation by growing SH-SY5Y cells on the hydrophobic surfaces of thermally-collapsed elastin-like polypeptide. After 4 days of culture, the relative proliferation of the cells within spheroids was approximately 92% of the values for monolayer cultures. As measured by quantitative assays for mRNA and protein expressions, the production of synaptophysin and neuronspecific enolase (NSE) as well as the contents of cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins are much higher in spheroids than in monolayer cells. Under the all-trans-retinoic acid (RA)-induced differentiation condition, spheroids extended neurites and further up-regulated the expression of synaptophysin, NSE, CAMs, and ECM proteins. Our data indicate that RA-differentiated SH-SY5Y neurospheroids are functionally matured neuronal architectures.

• Applied Chemistry for Engineering
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• v.5 no.5
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• pp.795-800
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• 1994

The detergencies of these new functional anionic surfactants, sodium monoglycerol ${\alpha}$-sulfonated alkanoates, were investigated and compared with those of two commercial surfactants, that is, sodium ${\alpha}$-sulfonated alkanoic acid methyl ester and sodium alkyl benzene sulfonate. According to the variation of the hydrophobic alkyl chain length, the order of detergency was shown to be $C_{16}$>$C_{18}$>$C_{14}$>$C_{12}$. From the comparision experiment for the detergency and the various fundamental properties of two other surfactants, it was found that sodium monoglycerol ${\alpha}$-sulfonated hexadecanonate has the most outstanding characteristics of detergency. Possibly this result shows light on its industrial application as a nonpolluting detergent.

• BMB Reports
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• v.32 no.6
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• pp.594-598
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• 1999

The Jun and Fos families of eukaryotic transcription factors form heterodimers capable of binding to their cognate DNA enhancer elements. We are interested in searching for inhibitors or antagonists of the binding of the Jun-Fos heterodimer to the activator protein-1 (AP-1) site. The basic-region leucine zipper (bZIP) domain of c-Fos was expressed as a fusion protein with glutathione S-transferase, and allowed to form a heterodimer with the bZIP domain of c-Jun. The heterodimer was bound to glutathione-agarose, to which were added radiolabeled AP-1 nucleotides. After thorough washing, the gel-bound radioactivity was counted. The assay is faster than the coventional electrophoretic mobility shift assay because the gel electrophoresis step and the autoradiography step are eliminated. Moreover, the assay is very sensitive, allowing the detection of picomolar quantities of nucleotides, and is not affected by up to 50% dimethylsulfoxide, a solvent for hydrophobic inhibitors. Curcumin and dihydroguaiaretic acid, recently known inhibitors of Jun-Fos-DNA complex formation, were applied to this Jun-GST-fused Fos system and revealed to decrease the dimer-DNA binding.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.65-76
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• 1992

The superoxide dismutase (SOD)-mimetic activities of copper complexes of a series of salicylic acid (SA) analogs were tested and compared to the activity of bovine erythrocyte SOD using ferricytochrome c reduction assay. Stability constants of copper complexes were measured potentiometrically using SCOGS2 program. In the presence of 10 g/l albumin, all the copper complexes lost their SOD mimetic activities. Multiple regression analysis was employed for the statistical comparisons between the SOD mimetic activity and their physicochemical properties. Correlation exists for the SOD mimetic activity and steric parameter $(E_s)$ and/or electronic parameter $({\Sigma}{\sigma})$ in xanthine/xanthine oxidase (XOD) system, demonstrating that E, plays a key role in SOD activity whereas ${\Sigma}{\sigma}$ influences it to a lesser extent. The protective effect of copper complexes against membrane damage was measured by counting D-glucose released frm $EG_s$. D-glucose and XOD were entrapped within $EG_s$ and acetaldehyde was used as a substrate for XOD. In this membrane model system using $EG_s$, hydrophobic parameter $({\Sigma}{\pi})$ is of most importance, producing parabolic equation while $E_s$, and ${\Sigma}{\sigma}$ appear to playa minor role in protection against D-glucose release. In summary, to design an efficient SOD mimetic, stability, steric factor, lipophilicity and redox potential should be considered.

• Journal of Applied Biological Chemistry
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• v.51 no.1
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• pp.36-44
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• 2008

Organic forms of arsenic (As) were determined through fractionation procedure of soil organic matter (SOM) in soil, sediments and mine tailing samples from the Myungbong, Dongil, and Okdong mining areas of southern Korea. An alkaline extraction method was applied to soil samples followed by the fractionation procedures of SOM by the DAX-8 and XAD-4 resin adsorption method. Major fraction of organic As species (42% to 98%) was found in acid-soluble fraction, whereas minor fraction (0.1 % to 67.8%) was present in the humic-associated As. In acid-soluble fractions, the transphillic- and hydrophilic-associated As were dominant in addition to As binding with humic and fulvic SOM. Arsenic binding was the strongest between pH 6 to 8 and reduced to about 70% at both low and high pH regions. The amount of both transphillic and hydrophillic associated As was less changed than humic and fulvic-associated As, in both low and high pH regions. This apparently indicates that As has stronger affinity towards hydrophillic rather than hydrophobic organics. From the experimental observation of As-binding SOM in natural soil, the ligand exchange model may be a feasible explanation of transphillic and hydrophillic affinity of As.

• Journal of Pharmaceutical Investigation
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• v.41 no.6
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• pp.323-329
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• 2011

In order to develop new protein carrier replacing poly(DL-lactic acid-co-glycolic acid) (PLGA) microspheres, succinylated pullulan acetate (SPA) was investigated to fabricate a long term protein delivery carrier. SPA microspheres loaded with lysozyme (Lys) as a model protein drug were prepared by a water/oil/water (W/O/W) double emulsion method. An acidity test of SPA copolymers after hydrolysis was performed to estimate the change of protein stability during releasing proteins from the microspheres. There was no pH change of SPA copolymers, but pH of PLGA polymers after hydrolysis was significantly decreased to around pH 2, indicating that the long-term stability of proteins released from SPA microspheres can be guaranteed. Loading efficiency of proteins into SPA microspheres was three times higher than those into conventional PLGA microspheres, indication of inducing stronger charge interaction between proteins and succinyl groups in SPA microspheres. Although initial burst behaviors were monitored in Lys-loaded SPA microspheres due to relatively strong hydrophilic succinyl segments in SPA microspheres, initial burst issues would be circumvented if the ratio of charge density of succinyl moieties and hydrophobic acetate groups is harmonically controlled. Therefore, in this study, a new attempt of protein delivery system was made and functional SPA was successfully confirmed as a new protein carrier.