Kayayyaki

Beta-D-2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) wani ƙayyadadden ƙayyadadden mai hana ƙwayar cutar hanta C (HCV) RNA kira a cikin sel Huh-7.Don hana HCV NS5B RNA polymerase, PSI-6130 dole ne a sanya fosforil zuwa nau'in 5'-triphosphate.An bincika phosphorylation na PSI-6130 da hana HCV NS5B.phosphorylation na PSI-6130 ta recombinant mutum 2'-deoxycytidine kinase (dCK) da uridine-cytidine kinase 1 (UCK-1) an auna ta ta yin amfani da wani nau'i na spectrophotometric dauki guda biyu.An nuna PSI-6130 a matsayin maɓalli don tsaftataccen dCK, tare da Km na 81 microM da kcat na 0.007 s-1, amma ba substrate don UCK-1 ba.PSI-6130 monophosphate (PSI-6130-MP) an samar da su sosai zuwa diphosphate kuma daga baya zuwa triphosphate ta hanyar sake haɗawa da mutum UMP-CMP kinase da nucleoside diphosphate kinase, bi da bi.An yi nazarin hana nau'in daji da maye gurbin (S282T) HCV NS5B RNA polymerases.Tsayayyen hanawa (Ki) na PSI-61 30 triphosphate (PSI-6130-TP) tare da nau'in enzyme na daji shine 4.3 microM.An sami irin wannan sakamakon tare da 2'-C-methyladenosine triphosphate (Ki = 1.5 microM) da 2'-C-methylcytidine triphosphate (Ki = 1.6 microM).NS5B tare da maye gurbin S282T, wanda aka sani don ba da juriya ga 2'-C-methyladenosine, PSI-6130-TP ya hana shi da inganci kamar nau'in daji.Haɗin PSI-6130-MP cikin RNA wanda aka tsarkake ta NS5B RNA polymerase ya haifar da ƙarewar sarkar.