Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases.
Structural analogues of nucleosides, nucleoside analogues (NA), are used in the treatment of cancer and viral infections. Antiviral NAs inhibit replication of the viral genome, whereas anticancer NAs inhibit cellular DNA replication and repair. NAs are inactive prodrugs that are dependent on intracellular phosphorylation to their pharmacologically active triphosphate form. The deoxyribonucleoside kinases (dNK) and ribonucleoside kinases (rNK) catalyze the first phosphorylation step, converting deoxyribonucleosides and ribonucleosides to their corresponding monophosphate form. The dNKs have been studied intensively, whereas the rNKs have not been as thoroughly investigated. This overview is focused on the substrate specificity, tissue distribution, and subcellular location of the mammalian dNKs and rNKs and their role in the activation of NAs.
Van Rompay
An R
AR
Department of Nephrology-Hypertension, University of Antwerp, 2610 Antwerp, Belgium.
Johansson
Magnus
M
Karlsson
Anna
A
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology; D003854:Deoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009705:Nucleosides / Q000378:metabolism / Q000494:pharmacology; D009928:Organ Specificity; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology; D012265:Ribonucleotides / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003854:Deoxyribonucleotides; D009705:Nucleosides; D011355:Prodrugs; D012265:Ribonucleotides; D017853:Phosphotransferases (Alcohol Group Acceptor); C020018:deoxyribonucleoside kinases