人喉表皮样癌细胞系（HEp-2细胞）和1型单纯疱疹病毒诱导的脱氧胸苷激酶：5-三氟甲基-2'-脱氧尿苷衍生物对其的抑制作用
HEp-2 cell- and herpes simplex virus type 1- induced deoxythymidine kinases: inhibition by derivatives of 5-trifluoromethyl-2'-deoxyuridine.
作者信息
Wigdahl B L, Parkhurst J R
出版信息
Antimicrob Agents Chemother. 1978 Sep;14(3):470-5. doi: 10.1128/AAC.14.3.470.
5-Trifluoromethyl-2'-deoxyuridine (F(3)Thd), its free base and nucleotide triphosphate derivative, along with the nucleotide monophosphate and nucleotide triphosphate of deoxythymidine (dThd), were investigated as inhibitors of HEp-2 cell deoxythymidine kinase (dTK) and herpes simplex virus type 1 (HSV-1)-induced dTK. 5-Trifluoromethyluracil did not inhibit cellular or viral dTK. F(3)dThd competitively inhibited phosphorylation of dThd by both the HEp-2 cell- and the HSV-1-induced dTK. The K(mapp) for dThd and the K(Iapp) for the alternate substrate, F(3)dThd, were 3.5 and 22.5 muM for the HEp-2 cell dTK and 63.5 and 71.0 muM for the HSV-1-induced dTK. dThd-5'-PPP at 10 muM inhibited HEp-2 cell- and HSV-1-induced dTK by 94 and 22%, respectively. In comparison, 10 muM F(3)dThD-5'-PPP inhibited HEp-2 cell- and HSV-1-induced dTK 95 and 15%, respectively. These data indicate that F(3)dThd-5'-PPP may mimic dThd-5'-PPP feedback regulation of cellular and viral dTK.
5-三氟甲基-2'-脱氧尿苷（F(3)Thd）、其游离碱和三磷酸核苷酸衍生物，以及脱氧胸苷（dThd）的一磷酸核苷酸和三磷酸核苷酸，被作为人喉表皮样癌细胞脱氧胸苷激酶（dTK）和单纯疱疹病毒1型（HSV-1）诱导的dTK的抑制剂进行了研究。5-三氟甲基尿嘧啶不抑制细胞或病毒dTK。F(3)dThd竞争性抑制人喉表皮样癌细胞和HSV-1诱导的dTK对dThd的磷酸化作用。对于人喉表皮样癌细胞dTK，dThd的表观米氏常数（K(mapp)）和替代底物F(3)dThd的抑制常数（K(Iapp)）分别为3.5和22.5 μM；对于HSV-1诱导的dTK，分别为63.5和71.0 μM。10 μM的dThd-5'-PPP分别抑制人喉表皮样癌细胞和HSV-1诱导的dTK 94%和22%。相比之下，10 μM的F(3)dThD-5'-PPP分别抑制人喉表皮样癌细胞和HSV-1诱导的dTK 95%和15%。这些数据表明，F(3)dThd-5'-PPP可能模拟dThd-5'-PPP对细胞和病毒dTK的反馈调节。
Zotero 插件