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논문 기본 정보
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- 한국미생물생명공학회 Journal of Microbiology and Biotechnology Journal of Microbiology and Biotechnology 제18권 제2호
- 발행연도
- 2008.1
- 수록면
- 328 - 333 (6page)
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A series of peptides binding to the HCV NS5B polymerase was selected from phage display peptide libraries. A conserved motif of Ser-Arg-X-Arg/Leu was identified among the selected peptides, and Pep2 (Trp-Ser-Arg-Pro-Arg-Ser- Leu) was chosen for further characterization. The binding of Pep2 to HCV NS5B in vivo was shown by a yeast twohybrid assay and by subcellular colocalization analysis using immunofluorescence confocal microscopy. The in vitro interaction was also confirmed by GST pulldown assay. The replication of the HCV 1b subgenomic replicon was efficiently inhibited by the presence of the peptide. By using a subtractive biopanning against Pep2, the binding site of the peptide was mapped at the pocket of Pro388 to Pro391 in the thumb subdomain of the polymerase. A yeast two-hybrid analysis using Pro388Ala and Pro391Ala mutants of NS5B confirmed the binding.
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참고문헌 (24)
참고문헌 신청
Adachi, T. / 2002 / The essential role of C-terminal residues in regulating the activity of hepatitis C virus RNAdependent RNA polymerase. Biochim. Biophys / Acta 1601 : 38 ~
Adda, C. G. / 2002 / Random sequence libraries displayed on phage: Identification of biologically important molecules. Comb. Chem / High Throughput Screen 5 : 1 ~ 14
Amin, A. / 2003 / Identification of constrained peptides that bind to and preferentially inhibit the activity of the hepatitis C viral RNA-dependent RNA polymerase / Virology
Beaulieu, P. L. / 2004 / Inhibitors of the HCV NS5B polymerase: New hope for the treatment of hepatitis C infections. Curr. Opin. Investig / Drugs 5 : 838 ~ 850
Bressanelli, S. / 1999 / Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc. Natl. Acad / Sci 96 : 13034 ~ 13039
Adda, C. G. / 2002 / Random sequence libraries displayed on phage: Identification of biologically important molecules. Comb. Chem / High Throughput Screen 5 : 1 ~ 14
Amin, A. / 2003 / Identification of constrained peptides that bind to and preferentially inhibit the activity of the hepatitis C viral RNA-dependent RNA polymerase / Virology
Beaulieu, P. L. / 2004 / Inhibitors of the HCV NS5B polymerase: New hope for the treatment of hepatitis C infections. Curr. Opin. Investig / Drugs 5 : 838 ~ 850
Bressanelli, S. / 1999 / Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus. Proc. Natl. Acad / Sci 96 : 13034 ~ 13039
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