• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1371-1376
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• 2006

BACE 1 ($\beta$-secretase), a membrane bound aspartic protease, is a key enzyme in the process of amyloid precursor protein (APP) into A$\beta$ peptide which is considered to play a causative role in Alzheimers Disease (AD). Here, we reported the synthesis and inhibitory activity of optically active 3-amino-4-aryl-piperidines.

• Natural Product Sciences
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• v.1 no.1
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• pp.55-60
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• 1995

In the course of evaluation of hepatoprotective components against alcohol-induced toxicity from Aloe spp., the methanol extract was found to cause a significant inhibition of rat liver cytosolic alcohol dehydrogenase activity. Systematic fractionation of active tractions monitored by bioassay led to isolation of four compounds; aloe-emodin, aloenin, ethylidene-aloenin and ${\beta}-sitosterol$, which were estimated as active principles for inhibition of c-ADH and c-ALDH activities in vitro.

• YAKHAK HOEJI
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• v.46 no.1
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• pp.24-29
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• 2002

Enoyl-Acyl Carrier Protein Reductase (Fabl) of bacteria is hem as an important target for new antibacterial drugs and plays a determinant role in completing cycles of elongation in type-H fatty acid synthase system. In this study, a fabI gene from Staphylococcus aureus 6538p cloned in pET-l4b vector and FabI protein was over-produced in Escherichaia coli BL2l (DE3). $NH_2$-terminal His-tagged FabI protein was purified by nickel-nitrilotriacetic acid (Ni-NTA) metalaffinity chromatography Purified 6xHis-tagged FabI showed a catalytic activity on tram - 2 - octenoyl - N -acethlcysteamine by utilizing NADPH as a cofactor. For the discovery of new FabI inhibitors from chemical libraries, a target-oriented screening system using a 96-well plate was developed. About 10,000 chemical libraries from Korea Chemical Bank wore tested in this screening system, and 26 chemicals (0.25%) among them showed an inhibitory activity against FabI enzyme. This result showed that a new screening system can be used for the discovery of new FabI inhibitors.

• Korean Journal of Plant Resources
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• v.14 no.1
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• pp.32-37
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• 2001

Mammalian tyrosinase plays an important role in the process of melanin polymer biosynthesis by catalyzing the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine(DOPA) and the oxidation of DOPA to dopaquinone. These processes are major determinant of human skin color and involved in localized hyperpigmentation. Therefore, the enzyme inhibitors have been of great concern as skin-whitening cosmetics. Methanol extracts of 174 oriental herbs were screened for the mushroom tyrosinase inhibitory activity.

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.301-305
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• 2003

Nitric oxide (NO) is an important bioactive agent that mediates a wide variety of physiological and pathophysiological events. NO overproduction by inducible nitric oxide synthase (iNOS) results in severe hypotension and inflammation. This investigation is part of a study to discover new iNOS inhibitors from medicinal plants using a macrophage cell culture system. Two sesquiterpenes (1 and 2) were isolated from Artemisia iwayomogi (Compositae) and were found to inhibit NO synthesis ($IC_{50} 3.64 \mu g/mL and 2.81 \mu$g/mL, respectively) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Their structures were identified as 3-Ο-methyl-iso-secotanapartholide (1) and iso-secotanapartholide (2). Compounds 1 and 2 inhibited the LPS-induced expression of the iNOS enzyme in the RAW 264.7 cells. The inhibition of NO production via the down regulation of iNOS expression may substantially modulate the inflammatory responses.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.183-183
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• 1998

Telomerase synthesizes telomeric DNA repeats onto chromosome ends de novo. Telomerase activation and telomere shortening in human somatic cells have been implicated in cell tumorigenesis and immortalization. In order to find the potential inhibitors against telomerase activitiy which can be used as potential anticancer agents, we screened about 100 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from methanol extracts. The inhibitory effects of these materials against telomerase enzyme activity were tested in 293T cell culture using telomeric repeat amplification protocol(TRAP). The incorporation of $\^$32/P-dGTP into amplified DNA was measured by adsorption to Whatman DE81 paper instead of using TRAP assay for screening the extracts of natural products. Strong effective compounds were not found in this study but DE81 filter spotting method may be a useful model for the screening. Some of the compounds which showed somewhat inhibitory effects had cytotoxic effects also.

• YAKHAK HOEJI
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• v.40 no.1
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• pp.65-71
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• 1996

Characterization of Polyphenol oxidase (PPO) in Perillae Folium, particullarly inhibitor studies were investigated. This enzyme was stable at pH 5.0 and the residual activity of PPO at ${\geq}$ ph 5.5 was estimated to be very low. PPO activity was decreased slightly by adding amino acid with catechol as a substrate, particullary PPO activity was inhibited markedly by cystein, histidine, lysine and arginine. In the absorption spectra of the product formed when catechol was oxidized by PPO, with a ${\lambda}_{max}$ at 410nm, the peak shifted toward ${\lambda}_{max}$ 520nm by addition of L-proline. At relatively low concentrations($10^{-3}M$), sulfite and dithiothreithol completely inhibited PPO activity. Inhibition of PPO activity by amino acids and inhibitors increased or decreased depending on the pH used to measure it.

• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3291-3296
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• 2010

A gelastatins (1), natural MMP inhibitors, and their hydroxamate analogues (2) in TACE enzyme evaluated for discovery of potent TACE inhibitors. We have employed molecular dynamics simulations to compute the relative free energy of hydration and binding to TACE for gelastatin (1) and its hydroxamate analogue (2). The relative free energy difference is directly described in this article using the free energy perturbation approach as a means to accurately predict the TACE inhibitor of gelastatin analogues. The results show that the good agreement between the experimental and theoretical relative free energies of binding, gelastatin hydroxamate (2) binds stronger to TACE by -3.37 kcal/mol. The desolvation energy costs significantly reduced binding affinity, hydroxamate group associated with high desolvation energy formed strong favorable interactions with TACE with more than compensated for the solvation costs and therefore led to an improvement in relative binding affinity.

• Bulletin of the Korean Chemical Society
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• v.23 no.7
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• pp.1003-1010
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• 2002

Caspase 3, a member of cysteine protease family, is well known as a major apoptosis effector and is involved in cell death as a result of ischemic diseases such as stroke and myocardial infarction, therefore the inhibition of caspase 3 may protect those apoptotic cell damages. During the high-throughput screening of the compounds from the Korea Chemical Bank, berberine derivatives (A and B), an isoquinoline alkaloid, have been identified as potential inhibitors for caspase 3. Based on this finding we carried out molecular modeling study to identify the pharmacophoric elements of berberine structure which interact with a substrate-recognition binding site of caspase 3 and came up with several novel scaffolds. In this report, we will discuss the molecular modeling, syntheses and the enzyme inhibitory activities of these novel compounds.

• BMB Reports
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• v.40 no.1
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• pp.7-14
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• 2007

Helicases are ubiquitous enzymes, which utilize the energy liberated during nucleotide triphosphate hydrolysis to separate double-stranded nucleic acids into single strands. These enzymes are very attractive targets for the development of new antibacterial compounds. The PcrA DNA helicase from Staphylococcus aureus is a good candidate for drug discovery. This enzyme is unique in the genome of S. aureus and essential for this bacterium. Furthermore, it has recently been published that it is possible to identify inhibitors of DNA helicases such as PcrA. In this report, we study the properties of recombinant PcrA from S. aureus purified from Escherichia coli to develop ATPase and helicase assays to screen for inhibitors.