• Title/Summary/Keyword: affinity binding

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Analysis of In Vivo Interaction of HCV NS3 Protein and Specific RNA Aptamer with Yeast Three-Hybrid System

  • HWANG BYOUNGHOON;LEE SEONG-WOOK
    • Journal of Microbiology and Biotechnology
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    • v.15 no.3
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    • pp.660-664
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    • 2005
  • We have previously isolated specific RNA aptamers with high affinity against the helicase domain of hepatitis C virus (HCV) nonstructural protein 3 (NS3). The RNA aptamers competitively and efficiently inhibited the helicase activity, partially impeding HCV replicon replication in human hepatocarcinoma cells. In this study, the RNA aptamers were tested for binding to the HCV NS3 proteins in eukaryotic cells, using a yeast three-hybrid system. The aptamers were then recognized by the HCV NS3 proteins when expressed in the cells, while the antisense sequences of the aptamers were not. These results suggest that the in vitro selected RNA aptamers can also specifically bind to the target proteins in vivo. Consequently, they could be potentially utilized as anti-HCV lead compounds.

Synthesis of Heterocyclic Substituted Pyridine Analogs as Potential Therapeutics for Neurodegenerative Diseases

  • Park, Haeil;Peter A. Crooks
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1999.04a
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    • pp.1-4
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    • 1999
  • The potential therapeutic benefit of nicotinic ligands in a variety of neurodegenerative pathologies involving the CNS has energized research efforts to develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands. In particular, there has been a concerted effort to develop nicotinic compounds with selectivity for CNS nAChRs as potential pharmacological tools in the management of these disorders. The characterization of other novel nicotinic ligands such as epibatidine. showing a marked increase in potency at nAChRs, has provided additional support for the development of potent, selective ligands at individual nAChR subtypes. We have developed and studied a number of nicotinic compounds to identify potential candidates exhibiting such selectivity. In the present study, we report the synthesis and biological evaluations of some azabicyclic and azatricyclic nicotine analogs to decipher the relationship among steric requirements of the nicotine's pyrrolidine ring system, binding affinity and subtype-selectivity.

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Ab Initio Study of Conformers of p-tert-Butylcalix[4]crown-6-ether Complexed with Alkyl Ammonium Cations

  • Choe, Jong-In;Jang, Suk-Kyu;Nanbu, Shinkoh
    • Bulletin of the Korean Chemical Society
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    • v.23 no.6
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    • pp.891-896
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    • 2002
  • The structures and energies of p-tert-butylcalix[4]crown-6-ether(1) in various conformers and their alkyl ammonium complexes have been calculated by ab initio HF/6-31G quantum mechanics method. We have tried to obtain the relative affinity of partial-cone and 1,3-alternate conformers of 1 for alkyl ammonium guests by comparison with its cone-shaped analogue. We have also calculated the relative complexation efficiency of these host-guest complexes focusing on the binding sites of $crown-\sigma-enther$ moiety or benzene-rings pocket of the host molecule 1. These calculations revealed that the crown moiey has better complexation efficiency than upper rim part of calyx[4]arene that is in similar trend to the cone-shaped complexes.

The Structure-Based Three-Dimensional Pharmacophore Models for Arabidopsis thaliana HPPD inhibitors as Herbicide

  • Cho, Jae Eun;Kim, Jun Tae;Kim, Eunae;Ko, Young Kwan;Kang, Nam Sook
    • Bulletin of the Korean Chemical Society
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    • v.34 no.10
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    • pp.2909-2914
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    • 2013
  • p-Hydroxyphenylpyruvate dioxygenase (HPPD) is a potent herbicide target that is in current use. In this study, we developed a predictive pharmacophore model that uses known HPPD inhibitors based on a theoretically constructed HPPD homology model. The pharmacophore model derived from the three-dimensional (3D) structure of a target protein provides helpful information for analyzing protein-ligand interactions, leading to further improvement of the ligand binding affinity.

Removal of Heavy Metal and ACE Inhibition of Yam Mucilage (마 점질물의 중금속 제거능과 ACE저해 효과)

  • 하영득;이삼빈;곽연길
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.4
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    • pp.751-755
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    • 1998
  • Functional properties of yam mucilage were investigated by physicochemical analysis. Yam mucilage was extracted from the root of yam and then separated into two fractions by its selective aggregation with isopropanol concentration. Each mucilge fraction showed the excellent binding properties with heavy metal ions Co, Cr and Cu. Cr showed the higher affinity with mucilage than Co and Cu at pH 6.3. In ACE inhibition, IC50 values of mucilage fraction 1 and 2 showed 8.99$\mu\textrm{g}$/${mu}ell$ and 7.1$\mu\textrm{g}$/${mu}ell$, respectively.

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Investigation of the Binding Affinity between Styrylquinoline Inhibitors and HIV Integrase Using Calculated Nuclear Quadrupole Coupling Constant (NQCC) Parameters (A Theoretical ab initio Study)

  • Rafiee, Marjan A.;Partoee, Tayyebe
    • Bulletin of the Korean Chemical Society
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    • v.32 no.1
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    • pp.208-212
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    • 2011
  • In this work, the calculated nuclear quadrupole coupling constants of $^{17}O$ in some styrylquinoline conformers were presented. The calculations were carried out to find the relationships between the charge distribution of styrylquinolines and their pharmaceutical behavior and to explore the differences among the electronic structures of some conformers of these potent HIV IN inhibitors. Furthermore, the HIV IN inhibitory of R1 and R2 rotamers was compared. On the basis of our results: - Charge density on oxygen atoms of carboxyl moiety has a dominant role in the drug activity. - The a conformer in which a divalent hydrogen atom is a link, has more capability in antiviral drug treatment. - The R1 conformer, as a $Mg^{+2}$ chelating agent, is better than R2 conformer and thus it is more inhibitor of HIV IN.

Production of Monoclonal Antibody against the Principal Metabolite of Cocaine, Benzoylecgonine (코카인의 주대사물인 벤조일에코닌에 대한 단일클론 항체의 제작)

  • Nam, Kyung-Soo;Kim, Jae-Wha;Oh, Eun-Suk;Choi, Myung-Ja;Choi, In-Seong;Chung, Tai-Wha
    • YAKHAK HOEJI
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    • v.36 no.2
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    • pp.188-190
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    • 1992
  • Two clones of monconal antibodies(Co-1 and Co-2) against BSA-benzoylecgonine(BSABE) were produced. Both monoclonal antibodies showed high binding affinity to BSA-BE. Observing from ELISA inhibition assay, Co-1 reacted only weakly with soluble benzoylecgonine, while Co-2 showed considerable reactivity with soluble benzoylecgonine.

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Cellular Resistance to Antifolates (항엽산제에 대한 세포의 저항성 기작)

  • 김정상
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.22 no.6
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    • pp.839-845
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    • 1993
  • One of the major problems of cancer chemotheraphy is the development of drug resistance in tumors, resulting in reduced responsiveness to subsequent treatments. The folate antagonists are being used to treat such diverse illnesses as cancer, leukemia, psoriasis, rheumatoid arthritis, etc. Previous studies have established that resistance to antifolates may occur in mammalian tumor cells by one or more of five mechanisms ; (a) an increase in the levels of the target enzyme, generally as a consequence of gene amplification ; (b) an alteration in the target enzyme, leading to an enzyme with a decreased binding affinity for the drug ; (c) a decrease in the uptake of the drug into the cells ; (d) increased extrusion of drugs out of cells ; (e) impaired ability to polyglutamylate the parent drug which is capable of being intracellularly metabolized to longer chain length.

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Electrochemical Detection of Single Nucleotide Polymorphism (SNP) Using Microelectrode Array on a DNA Chip (미소전극어레이형 DNA칩을 이용한 유전자다형의 전기화학적 검출)

  • 최용성;권영수;박대희
    • The Transactions of the Korean Institute of Electrical Engineers C
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    • v.53 no.5
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    • pp.286-292
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    • 2004
  • In this study, an integrated microelectrode array was fabricated on glass slide using microfabrication technology. Probe DNAs consisting of mercaptohexyl moiety at their 5-end were spotted on the gold electrode using micropipette or DNA arrayer utilizing the affinity between gold and sulfur. Cyclic voltammetry in 5mM ferricyanide/ferrocyanide solution at 100 ㎷/s confirmed the immobilization of probe DNA on the gold electrodes. When several DNAs were detected electrochemically, there was a difference between target DNA and control DNA in the anodic peak current values. It was derived from specific binding of Hoechst 33258 to the double stranded DNA due to hybridization of target DNA. It suggested that this DNA chip could recognize the sequence specific genes. It suggested that multichannel electrochemical DNA microarray is useful to develop a portable device for clinical gene diagnostic System.

Zika Virus: Discovering Effective Protease Inhibitors via Template-Based Modeling

  • Choi, Yongseok
    • Proceeding of EDISON Challenge
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    • 2016.03a
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    • pp.86-89
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    • 2016
  • The Zika virus, which is a member of the flavivirus genus, poses a serious threat to humanity because there is no vaccine or cure. Zika is suspected to cause microcephaly, and it is rapidly spreading throughout parts of Brazil. Surprisingly, there are no known protein structures for the virus which are essential for drug and vaccine development. This paper investigates the Zika virus's nonstructural proteins with template-based modeling by using GalaxyTBM/Refine/SC. GalaxyDock was used to examine the effectiveness of various known serine protease inhibitors in inhibiting the Zika viral protease. In testing five inhibitors, Kunitz soybean trypsin inhibitor showed the strongest binding affinity (-10.082 kcal/mol). This paper provides a rudimentary foundation for further drug discovery research regarding the Zika virus.

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