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2000 | 47 | 1 | 173-180
Article title

ATP-binding domain of NTPase/helicase as a target for hepatitis C antiviral therapy.

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To enhance the inhibitory potential of 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) vs hepatitis C virus (HCV) NTPase/helicase, ribavirin-5'-triphosphate (ribavirin-TP) was synthesized and investigated. Ribavirin-TP was prepared with the use of modified Yoshikawa-Ludwig-Mishra-Broom procedure (cf. Mishra & Broom, 1991, J. Chem. Soc., Chem. Commun, 1276-1277) involving phosphorylation of unprotected nucleoside. Kinetic analysis revealed enhanced inhibitory potential of ribavirin-TP (IC50=40 μM) as compared to ribavirin (IC50 > 500 μM). Analysis of the inhibition type by means of graphical methods showed a competitive type of inhibition with respect to ATP. In view of the relatively low specificity towards nucleoside-5'-triphosphates (NTP) of the viral NTPase/helicases, it could not be ruled out that the investigated enzyme hydrolyzed the ribavirin-TP to less potent products. Investigations on non- hydrolysable analogs of ribavirin-TP or ribavirin-5'-diphosphate (ribavirin-DP) are currently under way.
Physical description
  • Bernhard-Nocht-Institute for Tropical Medicine, Department of Virology, Bernhard-Nocht St. 74, 20359 Hamburg, Germany
  • Bernhard-Nocht-Institute for Tropical Medicine, Department of Virology, Bernhard-Nocht St. 74, 20359 Hamburg, Germany
  • Bernhard-Nocht-Institute for Tropical Medicine, Department of Virology, Bernhard-Nocht St. 74, 20359 Hamburg, Germany
  • Bernhard-Nocht-Institute for Tropical Medicine, Department of Virology, Bernhard-Nocht St. 74, 20359 Hamburg, Germany
  • Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
  • Bernhard-Nocht-Institute for Tropical Medicine, Department of Virology, Bernhard-Nocht St. 74, 20359 Hamburg, Germany
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, A. Pawińskiego 5a, 02-106 Warszawa, Poland
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, A. Pawińskiego 5a, 02-106 Warszawa, Poland
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