Structure-activity relationships for phosphorylation of nucleoside analogs to monophosphates by nucleoside kinases.

Abstract

The mammalian deoxyribonucleoside kinases thymidine kinase 1 and 2, deoxycytidine kinase and deoxyguanosine kinase phosphorylate deoxyribonucleosides and provide an alternative to de novo synthesis of DNA precursors. Their activities are essential for activation of several chemotherapeutically important nucleoside analogs. These four salvage kinase enzymes exhibit distinct substrate specificities for nucleoside analogs modified in the base and glycon moieties. In this review their. structure-activity relationships are discussed. Alternative routes for phosphorylation of nucleoside analogs are also reviewed, such as the phosphotransfer capacity of 5'-nucleotidase and protein kinases.