• Journal of the Korean Applied Science and Technology
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• v.14 no.2
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• pp.93-102
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• 1997

Isothiazoline derivatives is widely used to food, medical drug and industrial goods, cosmetics etcs, and it makes to restrain and to sterilize a breeding of microbe as a preservative and a sterilizing agent. It differs with the raw material of paraoxybenzoic acid derivatives or imidazolydinyl urea to be in use at present, on the efficacy and effect, and has various characteristics. This synthesis makes 3,3'-dithiodipropionic chloride to add a thionyl chloride in 3,3'-dithiodipropionic acid, and 3,3'-dithiodipropionic methyl amide makes to synthesize in a reflux reaction the mono methyl amine to 3,3'-dithiodipropionic chloride. And last synthesis becomes to make chlorination-cyclization molecule doing a reflux reaction in the temperature of $90{\sim}100^{\circ}C$ to mix excessively thionyl chloride and ethylene dichloride to 3,3'-dithiodipropionic methyl amide. The last synthesis material has got in the mixture of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazoline-3-one, and it is so-called isothiazoline derivatives. The purification of isothiazoline derivatives makes to fuse in ethyl acetate, and makes to decolorize and to deodorize in recrystallization. This experiment has been in synthesis and purification of isothiazoline derivatives, and has tried to measure on the antisepsis and sterilization function of microbe according to pH or content change.

• Journal of Integrative Natural Science
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• v.3 no.1
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• pp.49-53
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• 2010

Molecular docking is a critical event which mostly forms Van der waals complex in molecular recognition. Since the majority of developed drugs are small molecules, docking them into proteins has been a prime concern in drug discovery community. Since the binding pose space is too vast to cover completely, many search algorithms such as genetic algorithm, Monte Carlo, simulated annealing, distance geometry have been developed. Proper evaluation of the quality of binding is an essential problem. Scoring functions derived from force fields handle the ligand binding prediction with the use of potential energies and sometimes in combination with solvation and entropy contributions. Knowledge-based scoring functions are based on atom pair potentials derived from structural databases. Forces and potentials are collected from known protein-ligand complexes to get a score for their binding affinities (e.g. PME). Empirical scoring functions are derived from training sets of protein-ligand complexes with determined affinity data. Because non of any single scoring function performs generally better than others, some other approaches have been tried. Although numerous scoring functions have been developed to locate the correct binding poses, it still remains a major hurdle to derive an accurate scoring function for general targets. Recently, consensus scoring functions and target specific scoring functions have been studied to overcome the current limitations.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.257-263
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• 2013

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

• YAKHAK HOEJI
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• v.52 no.5
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• pp.412-417
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• 2008

BAY11-7082 was initially found to be an anti-inflammatory drug with NF-${\kappa}B$ inhibitory property. In this study, we evaluated modulatory function of BAY11-7082 on U937 cell-cell adhesion induced by CD29 (${\beta}1$-integrins). BAY11-7082 strongly blocked functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay. However, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. In particular, to understand molecular mechanism of BAY11-7082-mediated inhibition, the regulatory roles of CD29-induced actin cytoskeleton rearrangement under cell-cell adhesion and surface level of CD29 were examined using confocal and flow cytometic analysis. Interestingly, this compound strongly suppressed the molecular association of actin cytoskeleton with CD29 at cell-cell adhesion site. Moreover, BAY11-7082 also diminished surface levels of CD29 as well as its-associated adhesion molecule CD147, but not other adhesion molecules such as CD18 and CD43. Therefore, our data suggest that BAY11-7082 may be involved in regulating immune responses managed by CD29-mediated cell-cell adhesion.

• IMMUNE NETWORK
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• v.13 no.1
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• pp.16-24
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• 2013

CTLA-4Ig is regarded as an inhibitory agent of the T cell proliferation via blocking the costimulatory signal which is essential for full T cell activation. To improve applicability, we developed the CTLA-4Ig-CTKC in which the c-terminal lysine had been replaced by cysteine through single amino acid change. The single amino acid mutation of c-terminus of CTLA-4Ig was performed by PCR and was checked by in vitro transcription and translation. DNA construct of mutant form was transfected to Chinese hamster ovary (CHO) cells by electroporation. The purified proteins were confirmed by Western blot and B7-1 binding assay for their binding ability. The suppressive capacity of CTLA-4Ig-CTKC was evaluated by the mixed lymphocyte reaction (MLR) and in the allogeneic pancreatic islet transplantation model. CTLA-4Ig-CTKC maintained binding ability to B7-1 molecule and effectively inhibits T cell proliferation in MLR. In the murine allogeneic pancreatic islet transplantation, short-term treatment of CTLA-4Ig-CTKC prolonged the graft survival over 100 days. CTLA-4Ig-CTKC effectively inhibits immune response both in MLR and in allogeneic islet transplantation model, indicating that single amino acid mutation does not affect the inhibitory function of CTLA-4Ig. CTLA-4Ig-CTKC can be used in vehicle-mediated drug delivery system such as liposome conjugation.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2297-2304
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• 2013

A series of novel benzimidazole derivatives bearing a heterocyclic ring as oxadiazole (21-32), thiadiazole (33-34), triazole (35-36) were synthesized and evaluated for their activities against Coxsackie virus B3 and B6 in Vero cells. Compounds 21-26, 31-36 with moieties of 2'-pyridyl, 3'-pyridyl and 4'-pyridyl at the 2-position and oxadiazoles, thiadiazole, or triazole substituent at the 4- or 5-position generally displayed activities against CVB3 and CVB6. Especially compound 24 ($IC_{50}=1.08{\mu}g/mL$, SI = 61.7 against CVB3) was the promising candidate as lead compound for anti-enteroviral drug. It was observed in the incorporation of heterocyclic rings in benzimidazole at the 5-position could enhance their biological activities.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.385-393
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• 1998

Human neutrophil elastase (HNElastase, EC 3.4.21.37), a causative factor of inflammatory diseases, was purified by Ultrogel AcA54 gel filtration and CM-Sephadex ion exchange chromatography. HNElastase was inhibited by phenylbutazone in a concentration dependent manner up to 0.4 mM, but as the concentration increased, the inhibitory effect gradually diminished. Binding of phenylbutazone to the human neutrophil elastase caused strong Raman shifts at 200, 440, and 1194 $cm^{-1}$. The peak at 1194 $cm^{-1}$ might be evidence of the presence $of\;-N=N-{\Phi}$ radical. The core area of the elastase, according to the visual molecular model of human neutrophil elastase, was structurally stable. A deeply situated active center was at the core area surrounded by hydrophobic amino acids. Directly neighboring the active site was one positively charged atom and two atoms carrying a negative charge, which enabled the enzyme and the drug to form a strong interaction. Phenylbutazone may form a binding, similar to a key & lock system to the atoms carrying opposite charges near the active site of the enzyme molecule. Furthermore, the hydrophobicity of the surrounding amino acid near the active site seemed to enhance the binding strength of phenylbutazone. Binding of phenylbutazone near the active site may cause masking of the active site, preventing the substrate from approaching the active site and inhibiting elastase activity.

• Molecules and Cells
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• v.23 no.3
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• pp.379-390
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• 2007

We sequenced and characterized the complete mitochondrial genome of the Japanese fish tapeworm D. nihonkaiense. The genome is a circular-DNA molecule of 13607 bp (one nucleotide shorter than that of D. latum mtDNA) containing 12 protein-coding genes (lacking atp8), 22 tRNA genes and two rRNA genes. Gene order and genome content are identical to those of the other cestodes reported thus far, including its congener D. latum. The only exception is Hymenolepis diminuta in which the positions of trnS2 and trnL1 are switched. We tested a PCR-based molecular assay designed to rapidly and accurately differentiate between D. nihonkaiense and D. latum using species-specific primers based on a comparison of their mtDNA sequences. We found the PCR-based system to be very reliable and specific, and suggest that PCR-based identification methods using mtDNA sequences could contribute to the study of the epidemiology and larval ecology of Diphyllobothrium species.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.571-581
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• 2021

Towards the end of 2019, an atypical acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China and subsequently named Coronavirus disease 2019 (COVID-19). The rapid dissemination of COVID-19 has provoked a global crisis in public health. COVID-19 has been reported to cause sepsis, severe infections in the respiratory tract, multiple organ failure, and pulmonary fibrosis, all of which might induce mortality. Although several vaccines for COVID-19 are currently being administered worldwide, the COVID-19 pandemic is not yet effectively under control. Therefore, novel therapeutic agents to eradicate the cause of the disease and/or manage the clinical symptoms of COVID-19 should be developed to effectively regulate the current pandemic. In this review, we discuss the possibility of managing the clinical symptoms of COVID-19 using natural products derived from medicinal plants used for controlling pulmonary inflammatory diseases in folk medicine. Diverse natural products have been reported to exert potential antiviral effects in vitro by affecting viral replication, entry into host cells, assembly in host cells, and release. However, the in vivo antiviral effects and clinical antiviral efficacies of these natural products against SARS-CoV-2 have not been successfully proven to date. Thus, these properties need to be elucidated through further investigations, including randomized clinical trials, in order to develop optimal and ideal therapeutic candidates for COVID-19.

• Korean Journal of Veterinary Service
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• v.41 no.4
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• pp.239-244
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• 2018

Mycobacterium tuberculosis (M. tuberculosis) complex is the causative agent of tuberculosis (TB) in humans and bovine TB in mammalian hosts and grows very slowly. Selenium is a central molecule in nitrogen metabolism and an essential ingredient for all living cells and glutamic acid. The effects of selenium on the growth of M. tuberculosis, a representative slow-growing Mycobacterium species, were investigated and measured using the BacT Alert 3D System (MB/BacT System). Sodium selenate, at a final concentration of $10{\mu}g/mL$, reduced the average time-to detection (TTD) to 197.2 hours (95% confidence interval (CI), 179.6~214.8) from 225.1 hours (95% CI, 218~232.0) in the control culture media (P<0.05). The TTD did not increase with $\text\tiny{L}$-glutamate concentrations up to $10{\mu}g/mL$, but a significant reduction in the TTD was observed in the presence of $20{\mu}g/mL$ ${\text\tiny{L}}$-glutamate in culture media (P<0.05). In conclusion, selenate and ${\text\tiny{L}}$-glutamate enhance the growth of M. tuberculosis.