• Title/Summary/Keyword: Hepatitis C

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2'-Spirocyclopropyl-carbocyclic Nucleoside as a Novel Scaffold for Potent Anti-HCV Agents

  • Li, Hua;Yoo, Jin-Cheol;Hong, Joon-Hee
    • Bulletin of the Korean Chemical Society
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    • v.32 no.4
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    • pp.1146-1152
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    • 2011
  • The discovery of 2'-spirocyclopropyl-ribocytidine (J. Med. Chem. 2010, 53, 8150-8160) as a potent inhibitor of RNA synthesis by NS5B ($IC_{50}=7.3{\mu}M$), the RNA polymerase encoded by hepatitis C Virus (HCV), has led to the synthesis and biological evaluation of several carbocyclic versions of 2'-spiropropyl-nucleosides. The cyclopentenol intermediate 7 was successfully constructed via ring-closing metathesis (RCM) from divinyl 6. Spirocyclopropanation of enone 8 was effected by using (2-chloroethyl)-dimethylsulfonium iodide and potassium tert-butoxide to form the desired intermediate 9. The synthesized nucleoside analogues 21-24 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line. Among them, the cytosine nucleoside analogue 22 exhibited significant anti-HCV activity ($EC_{50}= 8.2{\mu}M$).

NanoBio-Technology for Practical Implementation in Drug Discovery

  • Min, Dal-Hui
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.02a
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    • pp.83-83
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    • 2013
  • To date, various nanobiotechnologicalapproaches for biosensors and drug development have been explosively studied. Despite of successful demonstrations, the new technologies hardly enjoyed routine applications in practical nanobiomedicine. Here, researchers trained at the interface of basic sciences and engineering are expected to play critical roles. In this tutorial, I will introduce recent studies which harness graphene derivatives for developing bioanalytical platforms to quantitatively analyze various enzyme activities and biomarkers. The systems rely on attractive interaction between graphene oxide and nucleic acids or phospholipids. Recently, one of the graphene-based bioassay system was applied to anti-viral drug screening and potent hit compounds were identified to treat hepatitis C. This study clearly shows that a new nanobio-technology can be routinely implemented in drug discovery, providing many advantages over conventional methods.

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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.

Antiretroviral Therapy 2006: Pharmacology, Applications, and Special Situations

  • Samuel, Rafik;Bettiker, Robert;Suh, Byung-Se
    • Archives of Pharmacal Research
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    • v.29 no.6
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    • pp.431-458
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    • 2006
  • As we approach the completion of the first 25 years of the human immunodeficiency virus(HIV) epidemic, there have been dramatic improvements in the care of patients with HIV infection. These have prolonged life and decreased morbidity. There are twenty currently available antiretrovirals approved in the United States for the treatment of this infection. The medications, including their pharmacokinetic properties, side effects, and dosing are reviewed. In addition, the current approach to the use of these medicines is discussed. We have included a section addressing common comorbid conditions including hepatitis B and C along with tuberculosis.

Effect of Astragali Radix on Low Density Lipoprotein Oxidation (황기의 저밀도지질단백질 (LDL)산화에 미치는 영향)

  • 김은정;양기숙
    • YAKHAK HOEJI
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    • v.45 no.5
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    • pp.529-536
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    • 2001
  • The root of Astragalus membranaceus Bunge (Leguminosae), which has been used for the treatment of hypertension, chronic hepatitis, duodenal ulcers, chronic nephritis and promotion of immunity in folk remedies. Several lines of evidence indicate that oxidative modification of low-density lipoprotein (Ox-LDL) may play an important role in atherogenesis. Hence, the role of antioxidants in the prevention of LDL oxidation needs to be determined. To investigate the antioxidant activity. we determined the MeOH ex. and fractions of Astragali Radix on the inhibition of LDL oxidation. The CH$_2$C1$_2$ and EtOAc orations inhibited the oxidative modification of LDL by a decrease in the lipid peroxide content and the electrophoretic mobility of LDL. Calycosin-7-0-$\beta$-D -glucoside which was isolated from EtOAc fraction inhibits the oxidative modification of LDL.

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CHANGES OF BLOOD PARAMETERS AFTER ESCALATING DOSE OF DA-3021 IN CYNOMOLGUS MONKEY

  • Kim, Choong-Yong;Heo, Jeong-Doo;Han, Su-Cheol;Jo, Yeong-Woo;Chung, Moon-Koo
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.194-194
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    • 2002
  • Interferon has therapeutic potential for a wide range of infectious and proliferous disorders such as chronic hepatitis C. However, it has drawbacks such as relatively short serum half-life and rapid clearance like other therapeutic proteins. The attachment of a polyethylene glycol (PEG) moiety to interferon is considered as one of the most promising solutions for its ability to extend the plasma residence time.(omitted)

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New Antimicrobial Agents for Children (소아청소년 영역에서의 새로운 항미생물제)

  • Eun, Byung Wook
    • Pediatric Infection and Vaccine
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    • v.16 no.1
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    • pp.6-12
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    • 2009
  • There are relatively few novel antimicrobial agents despite the dramatic increase in antimicrobial resistance and multiple drug resistance of clinical isolates worldwide. Vancomycin is still the most widely used antibiotic for treating resistant Gram-positive coccal infections in children, especially for methicillin-resistant Staphylococcus aureus. For children with Gram-positive coccal infections where vancomycin is not effective or older therapeutic agents cannot be tolerated, linezolid, quinupristin-dalfopristin or daptomycin may be useful in the appropriate clinical setting. For Gram-negative bacterial infections, new carbapenems await clinical application. Tebipenem pivoxil is a novel oral carbapenem undergoing clinical trials for acute otitis media in pediatric patients. Antiviral drug development is now progressing at the pace of antibiotic development 30 years ago. Newer antiviral agents used for the treatment of herpes viruses and hepatitis C virus infections in children are included in this review.

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Pharmacokinetics of DA-3021 (mono-PEGylated recombinant human interferon ($\alpha$-2a) after Subcutaneous Administrations to Experimental Animals

  • Jo, Yeong-Woo;Kim, Won-Geun;Choi, Yun-Kyu;Jeon, Hyun-Kyu;Kim, Dong-Hwan;Park, Beom-Soo;Lee, Sung-Hee;Kim, Won-Bae;Youn, Yu-Seok
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.424.1-424.1
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    • 2002
  • Interferon has therapeutic potential for a wide range of infectious and proliferative disorders such as chronic hepatitis C and malignant melanoma. However. it has some therapeutic problems as other protein therapeutics do. A variety of approaches have been developed to circumvent these problems. Among them. the attachment of a polyethylene glycol (PEG) moiety 10 interferon is considered as one of the most promising solutions for its ability of extending the plasma residence time. (omitted)

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Preparation of mono-PEGylated interferon alpha-2a and its properties

  • Jo, Yeong-Woo;Park, Beom-Soo;Kim, Won-Geun;Jeon, Hyun-Kyu;Choi, Yun-Kyu;Lee, Sung-Hee;Kim, Won-Bae;Na, Dong-Hee;Lee, Kang-Choon
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.418.1-418.1
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    • 2002
  • Recombinant interferon alpha is widely used for the treatment of diseases including chronic hepatitis C. However. it has drawbacks such as relatively short serum half-life and rapid clearance like other therapeutic proteins. Using PFGylFltioo which is one of the well-established methods to fulfill the requirements of a long-lasting form of protein. wIe prepared mono-PEG modified interferon alpha-2a in which polyethylene glycol moiety was covalently attached to the amino groups of interfelon alpha-2a. (omitted)

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