Antiviral Guanosine Analogs as Substrates for Deoxyguanosine Kinase: Implications for Chemotherapy

Abstract

A highly active form of human recombinant deoxyguanosine kinase (dGK) phosphorylated purine nucleoside analogs active against cytomegalovirus, hepatitis B virus, and human immunodeficiency virus, such as penciclovir, 2',3'-dideoxyguanosine and 3'-fluoro-2',3'-dideoxyguanosine. The antiherpesvirus drug ganciclovir, which is also used in gene therapy, was a substrate for dGK, but with low efficiency. ATP and UTP were both good phosphate donors, with apparent K-m values of 6 and 4 muM and V-max values of 34 and 90 nmol of dGMP/mg of dGK/min, respectively. With a mixture of 5 mM ATP and 0.05 mM UTP, which represent physiologically relevant concentrations, the activities of dGK with ganciclovir and penciclovir was 1% and approximately 10%, respectively, of that with dGuo, The levels of dGK in different tissues were determined with a selective enzyme assay and the total activities per gram of tissues were similar in liver, brain, heart, and thymus extracts. The fact that the cellular dGK enzyme can phosphorylate antiviral guanosine analogs may help to explain the efficacies and side effects of several forms of chemotherapy.

Published in

Antimicrobial Agents and Chemotherapy
2001, Volume: 45, number: 3, pages: 739-742

SLU Authors

• Herrström Sjöberg, Anita

  • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences
    

• Wang, Liya

  • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences
    

• Eriksson, Staffan

  • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Biochemistry and Molecular Biology
Medicinal Chemistry


Publication identifier

DOI: https://doi.org/10.1128/AAC.45.3.739-742.2001

Permanent link to this page (URI)

https://res.slu.se/id/publ/53114