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

• Autorzy: Borowski P. , Mueller O. , Niebuhr A. , Kalitzky M. , Hwang L.H. , Schmitz H. , Siwecka M.A. , Kulikowski T.
• Języki publikacji: EN

Abstrakty

EN

To enhance the inhibitory potential of 1-beta-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.

Słowa kluczowe

EN

enzyme inhibition; 5'-0-[-4-fluorosulphonylbenzoyl]adenosine; nucleoside-5'-triphosphate; ribavirin-5'-triphosphate; hepatitis C; nucleoside triphosphatase; trimethylphosphate; adenosine-5'[3-thiotriphosphate

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2000
• Tom: 47
• Numer: 1
• Opis fizyczny: p.173-180,fig.

Twórcy

autor

Borowski P.

• Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht St.74, 20359 Hamburg, Germany

autor

Mueller O.

autor

Niebuhr A.

autor

Kalitzky M.

autor

Hwang L.H.

autor

Schmitz H.

autor

Siwecka M.A.

autor

Kulikowski T.

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