• Genomics & Informatics
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• v.20 no.4
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• pp.47.1-47.13
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• 2022

Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection in nosocomial settings. As reported by the World Health Organization, carbapenem-resistant Enterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgent threat, and the greatest concern is that these bacterial pathogens may acquire genetic traits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expand antibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells; however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation protein domain, suggesting a new potential site as a drug target. DNA methylation regulates the attenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could be a novel antibiotic.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.109-109
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• 2001

In order to evaluate the neutral red uptake assay as an alternative method for phototoxicity test, we compared the potential of phototoxicity in vitro in cultured human fibroblasts and 3T3 fibroblast cells derived from Balb/c mice. Both fibroblasts were exposed to various known phototoxic chemicals (promethazine, neutral red, chlorpromazine, chlortetracycline, amiodarone, bithionol, 8-methoxypsoralen) and non-phototoxic chemical (ammonium laureth sulfate) and irradiated with 5 J/cm$^2$ of UVA.(omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.162-162
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• 2002

There has been many findings of natural, environmental or manufactered nonsteroidal substances shown to have estrogenic activity. Since estrogens affect reproduction and cellular development to cause disease in people or animals, chronic exposure may have a major impact on health.(omitted)

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.19-26
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• 2012

There are many cyclic peptides with diverse biological activities, such as antibacterial activity, immunosuppressive activity, and anti-tumor activity, and so on. Encouraged by natural cyclic peptides with biological activity, efforts have been made to develop cyclic peptides with both genetic and synthetic methods. The genetic methods include phage display, intein-based cyclic peptides, and mRNA display. The synthetic methods involve individual synthesis, parallel synthesis, as well as split-and-pool synthesis. Recent development of cyclic peptide library based on split-and-pool synthesis allows on-bead screening, in-solution screening, and microarray screening of cyclic peptides for biological activity. Cyclic peptides will be useful as receptor agonist/antagonist, RNA binding molecule, enzyme inhibitor and so on, and more cyclic peptides will emerge as therapeutic agents and biochemical tools.

• Korean Journal of Plant Resources
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• v.5 no.2
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• pp.95-103
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• 1992

Present anticancer drugs in the clinical side have not showed a conclusive effect of the chemotherapy for cancer patients. In order to find much more efficient antitumor agents fromnatural resources, various screening methods vivo and in vitro have been developed by manyresearchers. The intention of this paper is to provide an outline of some background on the tumorsystem in drug development of natural products, to review some screening programs for theevaluation of antitumor activity and to introduce the practical procedures of some antitumorscreening methods in vivo and in vitro. At the end of this paper, the current literatures related toantitumor natural products from higher plants at our laboratory are described.Key words'anticancer drugs, screening methods.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.183-189
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• 2008

The present study compared the feasibility of Caco-2 and MDCK cells as an efficient in-vitro model for the drug classification based on Biopharmaceutics Classification System (BCS) as well as an in-vitro model for drug interactions mediated by P-gp inhibition or P-gp induction. Thirteen model drugs were selected to cover BCS Class I{\sim}IV$ and their membrane permeability values were evaluated in both Caco-2 and MDCK cells. P-gp inhibition studies were conducted by using vinblastine and verapamil in MDCK cells. P-gp induction studies were also performed in MDCK cells using rifampin and the P-gp expression level was determined by western blot analysis. Compared to Caco-2 cells, MDCK cells required shorter period of time to culture cells before running the transport study. Both Caco-2 and MDCK cells exhibited the same rank order relationship between in-vitro permeability values and human permeability values of all tested model compounds, implying that those in-vitro models may be useful in the prediction of human permeability (rank order) of new chemical entities at the early drug discovery stage. However, in the case of BCS drug classification, Caco-2 cells appeared to be more suitable than MDCK cells. P-gp induction by rifampin was negligible in MDCK-cells while MDCK cells appeared to be feasible for P-gp inhibition studies. Taken all together, the present study suggests that Caco-2 cells might be more applicable to the BCS drug classification than MDCK-cells, although MDCK cells may provide some advantage in terms of capacity and speed in early ADME screening process.

• Korean Journal of Microbiology
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• v.38 no.4
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• pp.230-230
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• 2002

Class Ⅲ chitin synthases in filamentous fungi are important for hyphal growth and differentiation of several filamentous fungi. A genomic clone containing the full gene encoding Chs4, a class Ⅲ chitin synthase in Penicillium chrysogenum, was cloned by PCR screening and colony hybridization from the genomic library. Nucleotide sequence analysis and transcript mapping of chs4 revealed an open reading frame (ORF) that consisted of 5 exons and 4 introns and encoded a putative protein of 915 amino acids. Nucleotide sequence analysis of the 5′flanking region of the ORF revealed a potential TATA box and several binding sites for transcription activators. The putative transcription initiation site at -716 position was identified by primer extension and the expression of the chs4 during the vegetative growth was confirmed by Northern blot analysis. Amino acid sequence analysis of the Chs4 revealed at least 5 transmembrane helices and several sites for past-transnational modifications. Comparison of the amino acid sequence of Chs4 with those of other fungi showed a close relationship between P chrysogenum and genus Aspergillus.

• Journal of Microbiology and Biotechnology
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• v.17 no.10
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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.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.181-190
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• 2004

The docking and in silico ligand screening procedures can select small sets of lead -like candidates from large libraries of either commercially or synthetically available compounds; however, the vast number of such molecules make the potential size of this task enormous. To accelerate the discovery of drugs to inhibit several targets, we have exploited massively distributed computing to screen compound libraries virtually. The Korea@HOME project was launched in Feb. 2002, and one year later, more than 1200 PC's have been recruited. This has created a 31 -gigaflop machine that has already provided more than 1400 hours of CPU time. It has all owed databases of millions of compounds to be screened against protein targets in a matter of days. Now, the virtual screening software suitable for distributed environments is developed by BMD. It has been evaluated in terms of the accuracy of the scoring function and the search algorithm for the correct binding mode.

• Transactions of the Korean Society of Mechanical Engineers A
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• v.40 no.6
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• pp.581-585
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• 2016

Nowadays medical treatment service increase due to ageing population and improving the quality of life. Accordingly it is predicted that drug discovery market will expansion continuously. Therefore it is necessary that profit creation by drug discovery on the global market is important. HCS(High Contents Screening) has been emerging as a potential method to solve problems of the present drug discovery. This research is about liquid dispenser for HCS. The purpose of this research is to manufacture high performance liquid dispenser for HCS. The dispenser is designed to control 5 liquids separately. The liquid contact parts are designed disposably, biocompatibly and chemically inertly. Air curtain is equipped at the side of tip to dispense very small liquid volume and to prevent hanging drop on tip. Valving is performed by just controlling the pressure of the pressure driven pump without valve.