• BMB Reports
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• v.38 no.5
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• pp.517-525
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• 2005

Solid phase peptide synthesis method, which was introduced by Merrifield in 1963, has spawned the concept of combinatorial chemistry. In this review, we summarize the present technologies of solid phase peptide synthesis (SPPS) that are related to combinatorial chemistry. The conventional methods of peptide library synthesis on polymer support are parallel synthesis, split and mix synthesis and reagent mixture synthesis. Combining surface chemistry with the recent technology of microelectronic semiconductor fabrication system, the peptide microarray synthesis methods on a planar solid support are developed, which leads to spatially addressable peptide library. There are two kinds of peptide microarray synthesis methodologies: pre-synthesized peptide immobilization onto a glass or membrane substrate and in situ peptide synthesis by a photolithography or the SPOT method. This review also discusses the application of peptide libraries for high-throughput bioassays, for example, peptide ligand screening for antibody or cell signaling, enzyme substrate and inhibitor screening as well as other applications.

• BMB Reports
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• v.44 no.11
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• pp.705-712
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• 2011

Advances in the fields of proteomics and genomics have necessitated the development of high-throughput screening methods (HTS) for the systematic transformation of large amounts of biological/chemical data into an organized database of knowledge. Microfluidic systems are ideally suited for high-throughput biochemical experimentation since they offer high analytical throughput, consume minute quantities of expensive biological reagents, exhibit superior sensitivity and functionality compared to traditional micro-array techniques and can be integrated within complex experimental work flows. A range of basic biochemical and molecular biological operations have been transferred to chip-based microfluidic formats over the last decade, including gene sequencing, emulsion PCR, immunoassays, electrophoresis, cell-based assays, expression cloning and macromolecule blotting. In this review, we highlight some of the recent advances in the application of microfluidics to biochemistry and molecular biology.

• Journal of Microbiology and Biotechnology
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• v.27 no.5
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• pp.878-895
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• 2017

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

• Journal of Korean Biological Nursing Science
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• v.15 no.4
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• pp.202-209
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• 2013

Purpose: The purpose of this study is to investigate relationships among sun-screening agents use, bone health promotion behavior, and bone mineral density. Methods: The participants of this study were 105 female college students. The data were collected using a questionnaire about sun-screening agent use and bone health promotion behavior. Bone mineral density was measured with Ultrasound Bone Densitometer/Osteo Pro Series. Data were analyzed with the SPSS/Win 18.0 program. Results: The mean Z-score in female college students was $-1.04{\pm}1.26$, and the T-score was $-1.16{\pm}1.22$, 21.39% of the participants have osteopenia. Bone mineral density showed a significant correlation with weight. Bone mineral density showed no significant correlation between sun-screening agent use, and bone health promotion behavior. There was a significant correlation between protection power of sun-screening agents and the protection by clothes. Conclusion: According to the results of this study, we need to develop an intervention program for bone health promotion of female college students.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.479-483
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• 2004

An attempt was made to develop a proteinchip for screening of MITF (microphthalmia transcription factor) inhibitor. Binding of MITF to E-box causes transcription of several pigmenting genes including tyrosinase gene. We investigated binding of MITF and its DNA binding site (E-box) using a protein-DNA chip with various detection methods including flurorescence (Cyt3). SPR (surface plasmon resonance) and SPRi (surface plasmon resonance imaging). A fusion protein (MITF-Maltose Binding Protein) was attached on the glass plate by chemical modification. An inhibitory synthetic DNA oligomer, artificially designed based on the E-box sequence, inhibited the binding of MITF and E-box. These results showed the potentials of flurorescence-based MITF protein chip as a microarray for high throughput screening (HTS) system of depigmenting agents.

• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.330-337
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• 2001

Prickly pear(Opuntia ficus-indica var. saboten Makino, Cactaceae) is a tropical or subtropical plant, which is widely used as folk medicine for burned wound, edema and indigestion. Screening on the biological properties of the fruits(OFS-Fr) and stems(OFS-St) of the plant was carried out to prove the pharmacological significance. By hot plate and acetic acid-inducing writhing methods, significant analgesic effects of OFS-Fr and OFS-St were found in mice and anti-edemic effect was observed in carrageenin-induced inflammatory rats. However, the extracts showed no significant actions on central and autonomic nervous system and blood circulatory system, which imply no toxic effects to animal.

• Bulletin of the Korean Chemical Society
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• v.34 no.1
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• pp.231-236
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• 2013

Some cytotoxicity studies for the interpretation of the interaction between nanoparticles and cells are non-mechanistic and time-consuming. Therefore, non-biological screening methods, which are faster and simpler than in-vivo and in-vitro methods, are required as alternatives to current cytotoxicity tests. Here, we proposed a simple screening method for the analysis of the interaction between several AgNPs (bare-, citrate-, and polyvinylpyrrolidone-coating) and dye-containing vesicles acting as a biomimetic cell-membrane. The interaction between AgNPs and vesicles could be evaluated readily by UV-vis spectra. Absorbance deviation in UV-vis spectra revealed a large attraction between neighboring particles and vesicles. This was confirmed by (Derjagin, Landau, Verwey, and Overbeek) theory and DMF (dark-field microscopy) analysis. This proposed method might be useful for analyzing the cytotoxicity of nanoparticles with cell-membranes instead of in vitro or in vivo cytotoxicity tests.

• Applied Biological Chemistry
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• v.41 no.6
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• pp.471-476
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• 1998

A synthesis and the screening of new 2-iminothiazolines (IV) of which structures are modified based on a lead compound, thiazoline for development of new agrochemical fungicide were described. Bromination of acetoacetanilides (I) which were prepared by the reaction of diketene with anilines gave the corresponding ${\gamma}-bromoacetoactanilide\;(II)$. Treatment of II with N-phenyl-N'-methyl thiourea (III) afforded IV, structure of which was confirmed by various spectroscopic methods. Antifungal activity of the new IV was tested against six kinds of typical plant diseases (in vivo). The IV with aromatic substituents showed remarkable activity against the Pyricuraria oryzae at 250 ppm in primary screening. The candidates with control value over 90% in primary screening were selected and further tested for second screening at lower concentrations. The IV which has an electron-withdrawing substituent such as halogen, especially fluorine in aryl group showed a higher activity as compared to those with electron-donating group and meta substituent was for optimal position.

• Journal of Microbiology and Biotechnology
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• v.29 no.3
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• pp.419-428
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• 2019

Phytases are enzymes that can hydrolyze phytate and its salts into inositol and phosphoric acid, and have been utilized to increase the availability of nutrients in animal feed and mitigate environmental pollution. However, the enzymes' low thermostability has limited their application during the feed palletization process. In this study, a combination of B-value calculation and protein surface engineering was applied to rationally evolve the heat stability of Escherichia coli phytase. After systematic alignment and mining for homologs of the original phytase from the histidine acid phosphatase family, the two models 1DKL and 1DKQ were chosen and used to identify the B-values and spatial distribution of key amino acid residues. Consequently, thirteen potential amino acid mutation sites were obtained and categorized into six domains to construct mutant libraries. After five rounds of iterative mutation screening, the thermophilic phytase mutant P56214 was finally yielded. Compared with the wild-type, the residual enzyme activity of the mutant increased from 20% to 75% after incubation at $90^{\circ}C$ for 5 min. Compared with traditional methods, the rational engineering approach used in this study reduces the screening workload and provides a reference for future applications of phytases as green catalysts.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.