Alaabta

Beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) waa ka hortag gaar ah oo awood leh fayraska cagaarshow C (HCV) RNA ee unugyada Huh-7 replicon.Si loo joojiyo HCV NS5B RNA polymerase, PSI-6130 waa in lagu shubaa fosforyaal ah qaabka 5'-triphosphate.Fosforyaalka PSI-6130 iyo ka hortagga HCV NS5B ayaa la baaray.Fosforyaalka PSI-6130 by recombinant human 2'-deoxycytidine kinase (dCK) iyo uridine-cytidine kinase 1 (UCK-1) ayaa lagu cabiray iyadoo la adeegsanayo falcelinta spectrophotometric la isku daray.PSI-6130 waxaa la tusay inuu yahay substrate loogu talagalay dCK la safeeyey, oo leh Km of 81 microM iyo kcat 0.007 s-1, laakiin ma ahayn substrate UCK-1.PSI-6130 monophosphate (PSI-6130-MP) ayaa si wax ku ool ah fosfooraska loogu dhejiyay diphosphate ka dibna triphosphate by recombinant human UMP-CMP kinase iyo nucleoside diphosphate kinase, siday u kala horreeyaan.Ka-hortagga nooca duurjoogta ah iyo isbeddellada (S282T) HCV NS5B RNA polymerases ayaa la darsay.Joojinta joogtada ah ee gobolka (Ki) ee PSI-61 30 triphosphate (PSI-6130-TP) oo leh enzyme-ga nooca duurjoogta ah wuxuu ahaa 4.3 microM.Natiijooyin la mid ah ayaa lagu helay 2'-C-methyladenosine triphosphate (Ki=1.5 microM) iyo 2'-C-methylcytidine triphosphate (Ki=1.6 microM).NS5B oo leh isbeddelka S282T, kaas oo loo yaqaan in uu keeno iska caabin 2'-C-methyladenosine, waxaa hakiyay PSI-6130-TP si hufan sida nooca duurjoogta ah.Ku darida PSI-6130-MP ee RNA oo lagu darey NS5B RNA polymerase la safeeyey ayaa keentay joojinta silsiladda.