Logo image
HEp-2 Cell- and Herpes Simplex Virus Type 1- Induced Deoxythymidine Kinases: Inhibition by Derivatives of 5-Trifluoromethyl-2′-Deoxyuridine
Journal article   Open access   Peer reviewed

HEp-2 Cell- and Herpes Simplex Virus Type 1- Induced Deoxythymidine Kinases: Inhibition by Derivatives of 5-Trifluoromethyl-2′-Deoxyuridine

Brian L. Wigdahl and J. Rodney Parkhurst
Antimicrobial agents and chemotherapy, v 14(3), pp 470-475
Sep 1978
PMID: 213016
url
https://doi.org/10.1128/aac.14.3.470View
Published, Version of Record (VoR)Open Access (License Unspecified) Open

Abstract

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 μM for the HEp-2 cell dTK and 63.5 and 71.0 μM for the HSV-1-induced dTK. dThd-5′-PPP at 10 μM inhibited HEp-2 cell- and HSV-1-induced dTK by 94 and 22%, respectively. In comparison, 10 μM 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.

Metrics

4 Record Views
11 citations in Scopus

Details

Logo image