title: Inhibition of the helicase activity of the HCV NS3 protein by symmetrical dimeric bis-benzimidazoles.
abstract: 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.
authors.affiliation: Engelhardt Institute of Molecular Biology RAS, Vavilov Str. 32, Moscow 119991, Russia. ve_tun@mail.ru
authors.forename: Vera L
authors.initials: VL
authors.lastname: Tunitskaya
authors.forename: Anna V
authors.initials: AV
authors.lastname: Mukovnya
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Ivanov
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Gromyko
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ivanov
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Streltsov
authors.forename: Alexei L
authors.initials: AL
authors.lastname: Zhuze
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases