• Title/Summary/Keyword: combinatorial screening

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Combinatorial Solid Phase Peptide Synthesis and Bioassays

  • Shin, Dong-Sik;Kim, Do-Hyun;Chung, Woo-Jae;Lee, Yoon-Sik
    • 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.

Design and Combonatorial Synthesis of Selenoflavonoids and Indole Compounds for Neuroprotective Drug

  • Jeong, Jin-Hyun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.69-71
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    • 2003
  • As recent as 10 years ago, a method of developing new medicine was developed by a new compounding method moving away from an existing one. Combinatorial chemistry made it easier to combine various kinds of compounds in a very short time and with little effort from existing methods. Through combinatorial chemistry, a number of compounds were synthesized using HTS(High Throughput Screening), with many reports reaching a clinical stage in search of new candidate material. (omitted)

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Antibody Engineering

  • Hong, Hyo-Jeong;Kim, Sun-Taek
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.7 no.3
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    • pp.150-154
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    • 2002
  • Monoclonal antibodies (Mabs) have been used as diagnostic and analytical reagents since hybridoma technology was invented in 1975. In recent years, antibodies have become increasingly accepted as therapeutics for human diseases, particularly for cancer, viral infection and autoimmune disorders. An indication of the emerging significance of antibody-based therapeutics is that over a third of the proteins currently undergoing clinical trials in the United States are antibodies. Until the late 1980's, antibody technology relied primarily on animal immunization and the expression of engineered antibodies. However, the development of methods for the expression of antibody fragments in bacteria and powerful techniques for screening combinatorial libraries, together with the accumulating structure-function data base of antibodies, have opened unlimited opportunities for the engineering of antibodies with tailor-made properties for specific applications. Antibodies of low immunogenicity, suitable for human therapy and in vivo diagnosis, can now be developed with relative ease. Here, antibody structure-function and antibody engineering technologies are described.

Screening for bioactive compounds from natural products by ELISA assay

  • Iwanami, Naoko
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.34-37
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    • 1998
  • Combinatorial chemistry is one of the most interested topics in the area of drug discovery. One of the most important points is how to find a lead compound that gives the seed structure for designing of a combinatorial library. Natural products is suitable for searching a new bioactive compound with new structure. We have carried out systematic screening works to find natural products possessing the effects on inter-and intra-cellular signaling. Two hundreds extracts of medical plants and two thousands microbial culture broth samples have been tested for the induction and inhibition of IL-2 or IL-6 production (Fig. 1). ELISA is an efficient method for screenings from such a large number of samples. Now, we apply this method to search prion- binding agents.

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Microfluidic System Based High Throughput Drug Screening System for Curcumin/TRAIL Combinational Chemotherapy in Human Prostate Cancer PC3 Cells

  • An, Dami;Kim, Kwangmi;Kim, Jeongyun
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.355-362
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    • 2014
  • We have developed a fully automated high throughput drug screening (HTDS) system based on the microfluidic cell culture array to perform combinational chemotherapy. This system has 64 individually addressable cell culture chambers where the sequential combinatorial concentrations of two different drugs can be generated by two microfluidic diffusive mixers. Each diffusive mixer has two integrated micropumps connected to the media and the drug reservoirs respectively for generating the desired combination without the need for any extra equipment to perfuse the solution such as syringe pumps. The cell array is periodically exposed to the drug combination with the programmed LabVIEW system during a couple of days without extra handling after seeding the cells into the microfluidic device and also, this device does not require the continuous generation of solutions compared to the previous systems. Therefore, the total amount of drug being consumed per experiment is less than a few hundred micro liters in each reservoir. The utility of this system is demonstrated through investigating the viability of the prostate cancer PC3 cell line with the combinational treatments of curcumin and tumor necrosis factor-alpha related apoptosis inducing ligand (TRAIL). Our results suggest that the system can be used for screening and optimizing drug combination with a small amount of reagent for combinatorial chemotherapy against cancer cells.

Screening of SrO-B2O3-P2O5 Ternary System by Combinatorial Chemistry and QSAR (조합화학과 QSAR를 이용한 SrO-B2O3-P2O5 3원계 청색형광체 개발)

  • Yoo, Jeong-Gon;Back, Jong-Ho;Cho, Sang-Ho;Sohn, Kee-Sun
    • Journal of the Korean Ceramic Society
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    • v.42 no.6 s.277
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    • pp.391-398
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    • 2005
  • It is known that $BaMgAl_{10}O_{17}:Eu^{2+}(BAM)$ phosphors currently used have a serious thermal degradation problem. We screened $SrO-B_2O_3-P_2O_5$ system by a solution combinatorial chemistry technique in an attempt to search for a thermally stable blue phosphor for PDPs. A Quantitative Structure Activity Relationship (QSAR) was also obtained using an artificial neural network trained by the result fiom the combinatorial screening. As a result, we proposed a promising composition range in the $SrO-B_2O_3-P_2O_5$ ternary library. These compositions crystallized into a single major phase, $Sr_6BP_5O_{20}:Eu^{2+}$. The structure of $Sr_6BP_5O_{20}:Eu^{2+}$ was clearly determined by ab initio calculation. The luminescent efficiency of $Sr_6BP_5O_{20}:Eu^{2+}$ was 2.8 times of BAM at Vacuum Ultra Violet (VUV) excitation. The thermal stability was also good but the CIE color chromaticity was slightly poor.

Combinatorial Synthesis and Screening of the $Eu^{2+}$-activated Phosphors for LED in the System CaO-$Al_2O_3-SiO_2$

  • Park, Seung-Hyok;Yoon, Ho-Shin;Kim, Chang-Hae;Jang, Ho-Gyeom
    • 한국정보디스플레이학회:학술대회논문집
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    • 2004.08a
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    • pp.647-649
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    • 2004
  • We have synthesized phosphor in the system CaO-$Al_2O_3-SiO_2$ by combinatorial polymerized-complex method. The application of combinatorial synthesis and characterization of luminescent materials has been enlarged to identification and optimization in interesting new phosphor. In this study, we investigated luminescent properties of above-mentioned materials by excitation and emission spectra. In $Eu^{2+}$ activated $Ca_1Al_2Si_2O_8$ phosphor emit the blue light.

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Search for new phosphors for flat panel displays and lightings using combinatorial chemistry and computational optimization

  • Sohn, Kee-Sun;Jung, Yu-Sun;Cho, Sang-Ho;Kulshreshtha, Chandramouli
    • 한국정보디스플레이학회:학술대회논문집
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    • 2006.08a
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    • pp.33-38
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    • 2006
  • An evolutionary optimization process involving genetic algorithm and combinatorial chemistry was employed in an attempt to develop titanate-based red phosphors suitable for tri-color white light emitting diodes We screened a eight-cation oxide system including $(K,Li,Na)_x(Y,Gd,La,Eu)_yTi_zO_{\delta}$ in terms of luminescent efficiency. The combination of genetic algorithm and combinatorial chemistry was proven to enhance the searching efficiency when applied for phosphor screening. As a result, the composition was optimized to be $(Na_{0.92}Li_{0.08})(Y_{0.8}Gd_{0.2})TiO_4:Eu^{3+}$, The luminance of this phosphor was 110 % of that of well-known scheelite variant phosphor at an excitation of 400 nm.

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Rapid Analysis of Metabolic Stability and Structure of Metabolites in New Drug Development

  • Kim, Dong-Hyun
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.86-87
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    • 2002
  • Recent technological innovations in the drug discovery process such as combinatorial synthesis and high throughput screening have led to the identification of an increasingly large number of compounds at the hits-to-leads stage. Therefore, rapid and precise pharmacokinetic/metabolic screening is essential to enhance the tractability of selected leads and to minimize the risk of failure in the later stages of drug development. (omitted)

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