• Journal of Microbiology and Biotechnology
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• 제23권3호
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• pp.329-334
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• 2013

Uridinediphospho-N-acetylglucosamine enolpyruvyl transferase (MurA, E.C. 2.5.1.7) is an essential bacterial enzyme that catalyzes the first step of the cell wall biosynthetic pathway, which involves the transfer of an enolpyruvyl group from phosphoenolpyruvate to uridinediphospho-Nacetylglucosamine. In this study, novel inhibitors of Haemophilus influenzae MurA (Hi MurA) were identified using high-throughput screening of a chemical library from the Korea Chemical Bank. The identified compounds contain a quinoline moiety and have much lower effective inhibitory concentrations ($IC_{50}$) than fosfomycin, a wellknown inhibitor of MurA. These inhibitors appear to covalently modify the sulfhydryl group of the active site cysteine (C117), since the C117D mutant Hi MurA was not inhibited by these compounds and excess dithiothreitol abolished their inhibitory activities. The increased mass value of Hi MurA after treatment with the identified inhibitor further confirmed that the active-site cysteine residue of Hi MurA is covalently modified by the inhibitor.

• 약학회지
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• 제56권1호
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• pp.42-47
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• 2012

Soluble epoxide hydrolase (sEH) is a metabolic regulator of epoxyeicosatrienoic acids (EETs). EETs have many beneficial effects, vasodilation, anti-diabetes, anti-inflammation, cardiovascular protection, renal protection. Therefore, selective sEH inhibitors have a potential for treating these diseases. In the present study, screening methods for sEH inhibitors using PHOME ((3-phenyl-oxiranyl)-acetic acid cyano-(6-methoxynaphthalen-2-yl)-methyl ester) and 14-15-EET as substrates were established. To determine selectivity, microsomal epoxide hydrolase (mEH) inhibition assay was also developed using styrene oxide as a substrate of microsomal epoxide hydrolase. Our results obtained from 12-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]-dodecanoic acid (AUDA) used as a positive sEH inhibitor and valpromide used as a positive mEH inhibitor showed that these methods are useful for discovery of drug candidates.

• 대한화장품학회지
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• 제31권1호
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• pp.13-16
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• 2005

미백 물질 탐색 방법으로, MC1R 발현 인자인 Mitf (microrhthalmia transcription factor)를 이용한 protein chip을 적용하였다. MC1R promoter와 Mitf 결합의 저해 인자로써, DNA 상의 결합 부위인 E-box (CATGTG)와 유사한 서열을 가진 oligomer를 사용하였고, E-box 내외부의 서열 변화에 따른 저해율 또한 측정하였다. 그 결과 DNA-Mitf 결합 저해율에 있어서, E-box 서열 내 변화를 준 oligonucleotide 경쟁자는, E-box 이외의 서열 변화를 준 경쟁자보다 낮은 수치를 보였다.

• 약학회지
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• 제45권3호
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• pp.245-250
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• 2001

Aminoacyl tRNA synthetases of bacteria are known as potential targets for new anti-microbial agents. To isolate new inhibitors of bacterial methionyl-tRNA synthetases from natural sources, a new target-oriented screening system using whole cells which are over-expressing a target enzyme was developed. Approximately 8,000 culture broths of microorganisms from soils were tested by this screening system. Among them, ten culture broths was found to contain inhibitory activity against methionyl -tRNA synthetases of Escherichia coli. For the validation of the screening system, this new method was compared with in vitro enzymatic method. Seven out of 10 culture broths showed inhibitory activity against methionyl-tRNA synthetases of E. coli. This result showed that the new screening system was comparable to the enzyme assay. Thus we believe that our screening system as a new method can be applied for the screening of new antibiotics inhibiting bacterial methionyl-tRNA synthetases from natural products.

• Journal of Microbiology and Biotechnology
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• 제17권10호
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• pp.1712-1716
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• 2007

To generate new scaffold candidates as highly selective and potent cyelin-dependent kinase (CDK) inhibitors, structure-based drug screening was performed utilizing 3D pharmacophore conformations of known potent inhibitors. As a result, CR229 (6-bromo-2,3,4,9-tetrahydro-carbolin-1-one) was generated as the hit-compound. A computational docking study using the X-ray crystallographic structure of CDK2 in complex with CR229 was evaluated. This predicted binding mode study of CR229 with CDK2 demonstrated that CR229 interacted effectively with the Leu83 and Glu81 residues in the ATP-binding pocket of CDK2 for the possible hydrogen bond formation. Furthermore, biochemical studies on inhibitory effects of CR229 on various kinases in the human cervical cancer HeLa cells demonstrated that CR229 was a potent inhibitor of CDK2 ($IC_{50}:\;3\;{\mu}M$), CDKI ($IC_{50}:\;4.9\;{\mu}M$), and CDK4 ($IC_{50}:\;3\;{\mu}M$), yet had much less inhibitory effect ($IC_{50}:>20\;{\mu}M$) on other kinases, such as casein kinase 2-${\alpha}1$ (CK2-${\alpha}1$), protein kinase A (PKA), and protein kinase C (PKC). Accordingly, these data demonstrate that CR229 is a potent CDK inhibitor with anticancer efficacy.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.196-196
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• 2005

• 한국동물학회:학술대회논문집
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• 한국동물학회 1995년도 한국생물과학협회 학술발표대회
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• pp.299.2-299
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• 1995

No Abstract, See Full Text

• 한국균학회지
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• 제44권4호
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• pp.314-317
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• 2016

To develop a new anti-dementia acetylcholinesterase (AChE) inhibitor from edible mushrooms, AChE inhibitory activities were determined on water and ethanol extracts of various edible mushrooms from oriental medicine markets and agriculture markets. As a result, the 70% ethanol extract from Pholiota adiposa fruiting body had the highest AChE inhibitory activity of 30.6, and its water extract also had an AChE inhibitory activity of 23.8%. Therefore, we finally selected P. adiposa as a potent anti-dementia AChE inhibitor-containing mushroom. The AChE inhibitor of P. adiposa was maximally extracted when its fruiting body was treated with water for 3hr at $70^{\circ}C$ and 70% ethanol for 12 hr at $70^{\circ}C$, respectively.

• Biomolecules & Therapeutics
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• 제3권3호
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• pp.205-209
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• 1995

The novel compound KH 3218 was synthesized and evaluated for its ability to inhibit the gastric H$^{＋}$＋ $K^{＋}$ ATPase activity in vitro as well as to lessen gastric acid secretion in vivo. KH 3218 inhibited rabbit gastric H$^{＋}$＋ $K^{＋}$ ATPase in a concentration and time dependent manner. $IC_{50}$/ value was estimated to be about 15 $\mu$M. The inhibition of the H$^{＋}$＋ $K^{＋}$ ATPase by KH 3218 was blocked by sulfhydryl reducing agents, dithiothreitol or $\beta$-mercaptoethanol. The inhibition of the enzyme was not reversible by 50 fold dilution of the incubation mixtures, suggesting the irreversible nature of the inactivation. In the pylorus-ligated rift, KH 3218 reduced the total acid output as compared with the control. In addition, KH 3218 was capable of inhibiting H. pylori urease activity. These data suggest that KH 3218 is a potent inhibitor for H$^{＋}$＋ $K^{＋}$ ATPase activity as well as for gastric acid secretion, and has a potential to be developed as a novel antiulcer agent.

• 한국식품저장유통학회지
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• 제1권2호
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• pp.117-124
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• 1994

To investigate characterization of the ${\alpha}$-amylase inhibitors from cereals and legumes produced in Korea, inhibitory activities against ${\alpha}$-amylase with the inhibitor from barley(Hordeum vulgare), wheat(Triticum aestivun), black bean(Glycine max), bean(Cajanus cajon) and pea(Pisum sativum) were measured. Among the samples tested, inhibitors from naked barley and black bean(sabong) which showed the highest inhibitor activities of cereals and legumes, respectively, were characterized according to treatment condition. The results obtained were summarized as follows. During the germination of naked barley and black bean, ${\alpha}$-amylase activities were gradually increased but inhibitory activities against ${\alpha}$-amylases were decreased. Both activities were gradually decreased when naked barley and black bean were stored. More than 50% of activities of the inhibitors from naked barley and black bean were remained at 100$^{\circ}C$ for 15 min and 20 min, respectively, indicating that the inhibitor from black bean was more stable to heat than that of barley.