Inhibition of the helicase activity of the HCV NS3 protein by symmetrical dimeric bis-benzimidazoles.

Autor: Tunitskaya VL; Engelhardt Institute of Molecular Biology RAS, Vavilov Str. 32, Moscow 119991, Russia. ve_tun@mail.ru, Mukovnya AV, Ivanov AA, Gromyko AV, Ivanov AV, Streltsov SA, Zhuze AL, Kochetkov SN
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Sep 15; Vol. 21 (18), pp. 5331-5. Date of Electronic Publication: 2011 Jul 14.
DOI: 10.1016/j.bmcl.2011.07.018
Abstrakt: Dimeric bis-benzimidazoles (DBn) are the compounds specifically binding to A-T enriched sequences in the DNA minor groove. Due to this property they can inhibit DNA-dependent enzymes. We show that inhibition of the helicase activity of HCV NS3 protein by DBn was due to a novel mechanism, which involved direct binding of the ligands to the enzyme. The binding potency and inhibition efficacy depended on the length of the linker between the benzimidazole fragments. The most effective inhibitor DB11 partially prevented activation of NTPase activity of NS3 by poly(U) and increased affinity of the enzyme to the helicase substrate DNA.
(Copyright © 2011 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: