Zogulitsa

Beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) ndi inhibitor yeniyeni ya hepatitis C virus (HCV) RNA synthesis mu maselo a Huh-7 replicon.Pofuna kuletsa HCV NS5B RNA polymerase, PSI-6130 iyenera kukhala phosphorylated ku mawonekedwe a 5'-triphosphate.Phosphorylation ya PSI-6130 ndi kuletsa kwa HCV NS5B kudafufuzidwa.Phosphorylation ya PSI-6130 ndi recombinant human 2'-deoxycytidine kinase (dCK) ndi uridine-cytidine kinase 1 (UCK-1) inayesedwa pogwiritsa ntchito spectrophotometric reaction.PSI-6130 idawonetsedwa kuti ndi gawo laling'ono la dCK yoyeretsedwa, yokhala ndi Km ya 81 microM ndi kcat ya 0.007 s-1, koma sichinali gawo la UCK-1.PSI-6130 monophosphate (PSI-6130-MP) idapangidwa bwino phosphorylated ku diphosphate ndipo kenako ku triphosphate ndi recombinant human UMP-CMP kinase ndi nucleoside diphosphate kinase, motsatana.Kuletsa kwa mtundu wakutchire komanso wosinthika (S282T) HCV NS5B RNA ma polymerases adaphunziridwa.The steady-state inhibition constant (Ki) ya PSI-61 30 triphosphate (PSI-6130-TP) yokhala ndi enzyme yamtundu wakuthengo inali 4.3 microM.Zotsatira zofananazo zinapezedwa ndi 2'-C-methyladenosine triphosphate (Ki = 1.5 microM) ndi 2'-C-methylcytidine triphosphate (Ki = 1.6 microM).NS5B yokhala ndi kusintha kwa S282T, komwe kumadziwika kuti kumapereka kukana kwa 2'-C-methyladenosine, kudaletsedwa ndi PSI-6130-TP mogwira mtima ngati mtundu wakuthengo.Kuphatikizidwa kwa PSI-6130-MP mu RNA yopangidwa ndi NS5B RNA polymerase yoyeretsedwa idapangitsa kuti unyolo uthe.